Data on mTOR inhibitors (mTORi) in autoimmune cytopenia (AIC), in adults are scarce. We retrospectively analysed 30 cases of refractory or relapsing AIC treated with an mTORi-based therapy. Eleven warm autoimmune hemolytic anaemia, 10 autoimmune thrombocytopenia, 6 acquired pure red cell aplasia, 3 autoimmune neutropenia were included. Twenty were multilineage AIC (67%) and 21 were secondary AIC (70%). mTORi were associated with other therapies in 23 AIC (77%). Twenty-two AIC (73%) responded to mTORi-based therapy: 5 reached a partial response (17%) and 17 a complete response (57%). Survival without unfavourable outcome (failure, requirement of a new therapy, or death) was longer in multilineage AIC compared to single-lineage AIC (p = 0.049) with a median event-free survival of 48 versus 12 months. Median event-free survival was 48 months in secondary AIC and 33 months in primary AIC (p = 0.79). mTORi were discontinued in 4 patients (15%) for safety reasons and in 3 patients for patient's choice (12%). In conclusion, mTORi could be considered as an alternative or an add-on therapy in refractory or relapsing AIC in adult patients, especially in multilineage AIC.

We read with great interest the study by Zhou et al. entitled ‘A novel approach for characterization of KSHV-associated multicentric Castleman disease from effusions’ published in The British Journal of Haematology on the 4 October 2022.1 Kaposi sarcoma-associated herpesvirus (KSHV) + multicentric Castleman disease (MCD) is a life-threatening condition requiring prompt diagnosis that currently relies on a lymph node biopsy showing the presence of immunoglobulin (Ig)M+CD38+lambda+ KSHV-infected cells located in the mantle zone associated with plasma-cell rich features of CD. We previously reported the isolation of circulating IgM+CD38+lambda+ cells in the peripheral blood (PB) of three patients with active KSHV+ MCD.2 In this report, the authors first showed that flow cytometry could help differentiating KSHV+ MCD from primary effusion lymphoma (PEL), a KSHV-related malignant disorder carrying a dismal prognosis.3 In all, 11 patients presenting with effusions were analysed using a systematic antibody panel, and lambda-restricted CD38+ cells were isolated in eight of the 11 cases. No IgM staining was performed. These findings raise the question of the specificity of this analysis as PEL phenotype is extremely variable from one individual to another, as underlined by the authors. PEL are large cells expressing CD38, with a variable expression of the lambda light chain (three of 19 positive cases reported in Ref. [3]), CD138 (12/19 negative cases in Ref. [3]) and CD45 (one of 11 bright positivity in Ref. [1]) and the designed panel appears to be insufficient to formally differentiate KSHV-MCD from PEL. However, PEL is usually not a challenging diagnosis, excepted in cases with aberrant expression of T-cell markers that could suggest the possibility of T-cell lymphoma. The very peculiar cytological features and phenotype associated with very high human herpesvirus 8 (HHV8) DNA levels and complex karyotype easily prompt the diagnosis. The inconstant and unnecessary association with Epstein–Barr virus (EBV) is an additional argument for the diagnosis.3, 4 In contrast, KSHV-related diffuse large B-cell lymphoma, not otherwise specified often associated with MCD lesions5 could represent a challenging differential diagnosis as malignant cells express CD38 and exhibit an IgM lambda-restricted phenotype similar to that observed on MCD plasmablasts. This issue has not been addressed in this study. The authors then showed that lambda-positive cells were KSHV-infected using an antibody directed against the latent nuclear antigen (or LNA-1) by flow cytometry. The experimental conditions have not been detailed in the Material and Methods nor in the Data S1 sections and the antibody has not been referenced. Staining of an isotype control antibody has not been shown. As shown in Figure 1, we did not find any commercially available LNA antibody suitable for flow cytometry, notably because of a lack of specificity on KSHV+ cell lines (KSHV+EBV− PEL cell lines BC-3 and BCP1) when compared to KSHV− cell line (BJAB cell line, a KSHV−EBV− Burkitt-like lymphoma cell line). Immunohistochemistry prevents using multiparametric staining and we therefore developed a flow-fluorescent in situ hybridisation technique allowing the identification of latent and lytic KSHV transcripts coupled with an extracellular multiparametric staining.6 This method should therefore be preferred when assessing KSHV infection on liquid samples. The authors finally showed that KSHV-infected cells could be detected from PB or bone marrow of patients with active KSHV+ MCD (n = six) and KSHV inflammatory cytokine syndrome (n = three). The number of samples is relatively small, but the results are in line with our findings on the PB of 18 patients with KSHV+ MCD flare6 where we could detect KSHV-infected cells in up to 80% of the samples. It would have been interesting to analyse the PB of KSHV+ patients who had lambda-restricted cells within effusions. The lambda-restricted cells described in this work were called plasmablasts (or lambda-restricted plasmablasts [LRPs]), as KSHV+ MCD was formerly called the ‘plasmablastic’ variant due to the morphology of the large cells infected by KSHV/HHV8 found in the lesions. We performed a comparative phenotypic analysis between KSHV-infected cells found in KSHV+ MCD and conventional plasmablasts found in various reactive conditions and showed these cells differed from conventional plasmablasts and, therefore, should be better denominated as KSHV-infected viroblasts (KIVs) rather than plasmablasts. Of note, conventional plasmablasts were mainly IgG+ and uniformly expressed CD27 and CD86, whereas KIV were IgM+ and had a variable expression of CD27 and CD86.6 Altogether these novel findings require further technical investigations and validation on larger cohorts but represent interesting future directions in the understanding of KSHV-related lymphoproliferative disorders. A. Vanjak and D. Boutboul wrote the manuscript. A. Dossier, L. Galicier, R. Bertinchamp, E. Oksenhendler, and D. Boutboul contributed to the patient recruitment and management. A. Vanjak, M. Garzaro, S. Knapp, M.-A. Silvestrini, G. Martin de Fremont and D. Boutboul performed the experiments and analysed the data. V. Meignin and J. Calvani performed pathological reviewing of MCD samples. D. Boutboul supervised the project. All the authors critically reviewed the manuscript. Eric Oksenhendler is a consultant for Eusapharma. The other authors have no potential conflict of interest to declare. Data S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Castleman disease is a group of rare disorders characterized by lymph node enlargement, specific microscopic changes to the lymph nodes, and a broad range of symptoms and laboratory findings. The two main subtypes are unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). The multicentric subtype can be further classified into two categories: HHV-8 positive multicentric Castleman disease and idiopathic multicentric Castleman disease (iMCD). In the United States (US), the annual incidence of Castleman disease (CD) has been estimated to range from 6500 to 7700 in a 2014 study. Approximately 75 percent were estimated to be unicentric CD and the remaining 25 percent were estimated to be split between HHV-8-associated MCD or HHV-8-negative/idiopathic MCD. Diagnostic criteria for iMCD have been established by an international working group of pediatric and adult pathology and clinical experts. The proposed consensus criteria require characteristic histopathologic findings on lymph node biopsy, enlargement of multiple lymph node regions, the presence of multiple clinical and laboratory abnormalities, and the exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. © 2022 Published by Elsevier Masson SAS on behalf of Société nationale française de médecine interne (SNFMI).

Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.

Mantle cell lymphoma (MCL) is a rare subtype of lymphoid malignancy, representing 5%–7% of adult-onset non-Hodgkin lymphoma (NHL) in Western countries, but with a rising incidence.1 Most patients with MCL have an aggressive disease. However, 10%–15% of the patients have a more indolent course and can remain free of treatment for several years. Despite major therapeutic advances, the prognosis of MCL remains poor, with a median overall survival (OS) of 4–9 years.2 Patients living with human immunodeficiency virus (HIV) remain at increased risk of developing NHL.3 Despite prognostic improvement since the introduction of combination anti-retroviral therapy (cART), NHL remains the most common cancer-related cause of death in HIV-infected patients.4 Most HIV-associated NHLs are high-grade B-cell lymphomas. Low-grade lymphomas are less common, and to our knowledge, only one HIV-associated MCL (HIV-MCL) case has been reported to date, in the pre-cART era.5 Among the 976 patients with NHL enrolled in the HIV-lymphoma cohort between June 1996 and June 2021 with a stable median enrolment of 35 NHL-HIV per year (21–49), eight patients (0.8%) were diagnosed with MCL (Table 1). The estimate incidence rate was 0.7/1000 patient-years during the 10 786 patient-years of observation time (Table S1). HIV infection was diagnosed prior to the diagnosis of MCL in all patients, with a median duration of 14.5 years. All the patients were treated with cART. One patient (#2) had a non-progressive leukaemic presentation with moderate lymphocytosis (4.21 × 109/l) and seven patients had an aggressive course. The morphology pattern revealed classic cytological variant in seven cases, and blastoid variant in one (#3). Overexpression of cyclin D1 was detected by immunohistochemistry in all patients, and the t(11;14)(q13;q32) translocation in three of three patients. All but one patient (#2) received chemotherapy. Treatment, outcome, and cause of death are detailed in Table 1. After a median (interquartile range) follow-up of 6.5 (4–24) months, six patients had died. The median OS was 7.7 months (Figure 1). Two patients died from coronavirus disease 2019 (COVID-19) infection while in complete remission (CR; #6 and #7). One of them died before vaccination and the other after a single injection of BNT162b2 vaccine. This study represents the only series of HIV-MCL reported to date. MCL accounts for <1% of NHL in the HIV-lymphoma cohort, while it represents 5%–7% in the general population.6 This lower prevalence could be explained by the relatively young age of the HIV-infected population. In line with the general population, the median age of HIV-infected patients at MCL diagnosis was >60 years. The proportion of HIV-infected patients aged ≥65 years is projected to nearly triple between 2010 to 2030, from 8.5% to 21.4% in Western countries.7 The number of patients enrolled in the HIV-lymphoma cohort was relative stable over time, with an increased incidence rate of MCL during recent years as half of the cases were diagnosed in the past 4 years. As the incidence of MCL is rising in the general population and life expectancy is increasing among HIV individuals, one could expect an increasing incidence of HIV-MCL in the coming years. Demographic and clinical features of patients with HIV-MCL are very close to that of patients with non-HIV-MCL. The observed predominance of males represents the HIV population demography. One patient presented with asymptomatic leukaemic MCL and is still treatment-free after 11 years. The seven other patients required systemic therapy because of disease-related symptoms, a proportion similar to that reported in non-HIV-MCL.2 At MCL diagnosis, patients had a long duration of controlled HIV infection on cART with mild immunodeficiency. The previously reported case in pre-cART era, also occurred in a patient with a long-lasting HIV infection (6 years) and a relatively high CD4+ T-cell count (0.36 × 109/l).5 Treatment of HIV-associated lymphoma has markedly improved during the last decades. Anti-retroviral therapy-induced immune restoration and decreased drug interactions allow a similar therapeutic approach of lymphoma in HIV-infected and uninfected patients. Addition of rituximab and autologous stem cell transplantation (ASCT) is now feasible, with acceptable toxicity, in selected HIV-infected patients.8 The current guidelines of MCL treatment in the general population recommend front-line intensive chemo-immunotherapy containing high-dose cytarabine and rituximab, followed by ASCT consolidation for young physically fit patients, and the use of maintenance rituximab after ASCT or after chemo-immunotherapy in elderly patients.6, 9-11 In the present series, two patients did not receive such intensive therapy; one patient (#1) was diagnosed before current recommendations and one patient (#8) died before receiving rituximab. Among the four eligible patients, two patients with early progression did not receive consolidation with ASCT. Two patients received maintenance rituximab therapy. A poor outcome, with a median OS of 6.2 months, was observed in the seven treated patients. In non-HIV-infected patients, the median OS ranges between 4 and 9 years, and is not reached with recent regimens.2, 6 The 4-year OS even reached 89% after ASCT plus rituximab maintenance.11 The cause of death was progressive disease in four patients, and no patient died from treatment toxicity nor HIV-related complications. The COVID-19 outbreak is undoubtedly a partial explanation for this poor outcome, as two out of the four patients alive at the epidemic outbreak had received rituximab and/or ASCT during the preceding 6 months and died, while in CR, from COVID-19 infection. This is in accordance with a recent meta-analysis that reported a high mortality rate in adults with haematological malignancy and COVID-19 infection, especially for those receiving B-cell depleting treatment.12 In conclusion, HIV-MCL is probably more associated with the ageing population than with HIV-induced immunodeficiency and therefore its incidence is expected to increase in the coming years. Despite a relatively young age at diagnosis and low Mantle cell lymphoma International Prognostic Index score, a poor outcome was observed in HIV-infected patients. This result should be interpreted with caution due to the small number of patients and the context of COVID-19 pandemic and should not prevent treating these patients according to the current guidelines with up-front ASCT when feasible and rituximab maintenance therapy. Rémi Bertinchamp and Laurence Gérard wrote the manuscprit. Rémi Bertinchamp, Margaux Garzaro, David Boutboul, Lionel Galicier, Mohammed El Hadi Djerad, Willy Rozenbaum, Philippe Simon, Eric Oksenhendler and Laurence Gérard contributed to patient recruitment and management. Rémi Bertinchamp and Laurence Gérard extracted and analysed the data. Eric Oksenhendler, David Boutboul, Véronique Meignin, Lionel Galicier provided critical revision of the manuscript. Véronique Meignin and Julien Calvani performed pathological analysis. All authors reviewed the manuscript. Eric Oksenhendler is consultant for Eusapharma and CSL Behring. The remaining authors declare no conflict of interest to disclose. Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Purpose Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia. Methods Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed. Results A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype. Conclusion Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.

Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus–associated PELs, including 14 EBV + and 5 EBV − PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV + and EBV − cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV + and EBV − PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P =0.62).

Castleman disease is a group of rare disorders characterized by lymph node enlargement, specific microscopic changes to the lymph nodes, and a broad range of symptoms and laboratory findings. The two main subtypes are unicentric Castleman disease ( UCD) and multicentric Castleman disease (MCD). The multicentric subtype can be further classified into two categories: HHV- 8 positive multicentric Castleman disease and idiopathic multicentric Castleman disease (iMCD). In the United States (US), the annual incidence of Castleman disease ( CD) has been estimated to range from 6500 to 7700 in a 2014 study. Approximately 75 percent were estimated to be unicentric CD and the remaining 25 percent were estimated to be split between HHV-8-associated MCD or HHV-8-negative/idiopathic MCD. Diagnostic criteria for iMCD have been established by an international working group of pediatric and adult pathology and clinical experts. The proposed consensus criteria require characteristic histopathologic findings on lymph node biopsy, enlargement of multiple lymph node regions, the presence of multiple clinical and laboratory abnormalities, and the exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. (c) 2022 Published by Elsevier Masson SAS on behalf of Societe nationale francaise de medecine interne (SNFMI).

Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.

PURPOSE 18F-labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) data in HIV-associated Hodgkin lymphoma (HIV-HL) are scarcely reported. In addition to the description of the characteristics of both baseline and interim 18F-FDG PET-CT examinations (PET1 and iPET, respectively), the aim of this study was to assess the prognostic value of PET1 and previously identified clinical parameters in this population. PATIENTS AND METHODS PET1 of 109 patients with HIV-HL, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy regimen since 2007, and 104 iPET were centrally reviewed. All the patients were enrolled in an ongoing prospective single-center cohort of HIV-associated lymphoma. RESULTS Most patients had a disseminated disease according to the Ann Arbor classification (30% stage III and 43% stage IV), with especially bone marrow and liver as extranodal localizations. After a median follow-up of 6.7 years, 12 patients relapsed (11%) and 13 died (12%). Five-year progression-free survival (PFS) was 75.1%, and 5-year overall survival was 86.1%. Median total metabolic tumor volume (TMTV) was 121.4 cm3. The optimal TMTV cutoff identified for prognostic analysis was 527 cm3, with a 2-year PFS of 71% in the 20 patients with TMTV > 527 cm3, compared with 91% in the 89 patients with TMTV ≤ 527 cm3 ( P = .004). On multivariate analysis, a high TMTV was the only parameter independently associated with PFS. CONCLUSION In this large series of HIV-HL patients with a homogeneous management, high TMTV on PET1 examination was associated with a poor prognosis.

Idiopathic multicentric Castleman disease (iMCD) is a non-clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD-not otherwise specified (iMCD-NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD-NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD-NOS, respectively. The two-year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients.

Key Points Autoimmune hypoglycemia belongs to the clinical spectrum of HHV8+ MCD and rituximab is an effective treatment of this condition. This rare complication is related to autoantibodies directed toward the insulin receptor and activating the insulin signaling pathway.

Point of care ultrasound (PoCUS) with pocket-size devices is an efficient and safe imaging modality that became a standard of care in various clinical settings. However, its implementation in hematology has never been evaluated so far. We conducted a prospective monocentric study aiming to harvest data on its usage and to assess its diagnostic and interventional performance in improving the accuracy of basic physical examination in hematological patients. After a focused training program, six hematologists were trained and conducted this study. Sixty-two patients were included. Only in 19 cases, further specialized imaging was required, whereas, in 43 patients PoCUS was sufficient to address the clinical inquiries. The use of PoCUS devices was assessed for its performance difficulty and usefulness perception with satisfactory outcomes. This study represents a proof-of-concept application of PoCUS in hematology, suggesting benefits over the physical examination.KEY POINTSPoCUS is particularly attractive in a hematological setting because able to improve the accuracy of physical examination.A hematology-focused training in PoCUS using handheld devices can allow hematologists to perform bed-side diagnostic and interventional US-based exams.

Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disease of unknown etiology. Deciphering mechanisms involved in CD pathogenesis may help improving patients’ care. Six cases of stereotyped sub‐diaphragmatic iMCD affecting lower limb‐draining areas and associated with severe and often ulcerative lower extremity chronic dermatological condition were identified in our cohort. Pathological examination revealed mixed or plasma‐cell type MCD. In three patients, shotgun metagenomics failed to identify any pathogen in involved lymph nodes. Antibiotics had a suspensive effect while rituximab and tocilizumab failed to improve the condition. This novel entity requires a specific approach and exclusion of potentially harmful immunomodulation.

Background: The aim of this study was to evaluate the prognostic value of persistent retroperitoneal fibrosis FDG uptake using FDG/PET CT in patients with idiopathic retroperitoneal fibrosis (IRF). Methods: In this monocentric retrospective cohort study, all patients admitted for IRF from January 2009 to December 2017 underwent a FDG/PET CT at diagnosis and during follow up. Metabolic activity of IRF was assessed by retroperitoneal fibrosis FDG uptake measured as maximal standardized uptake value (SUVmax). The primary outcome was IRF relapse rate during follow-up. Results: 23 consecutive patients (54.7 [36.9-89] years, 73.9% of men) diagnosed with IRF had FDG/PET CT imaging performed at diagnosis, 3.1 [1-8.7] months (i.e 1st evaluation) and 10.4 [4.9-17.5] months (i.e 2nd evaluation) after diagnosis. High FDG retroperitoneal fibrosis uptake was present in all patients at diagnosis (SUVmax 6.5 [3.8-11.9]) and persisted in 16 (69.6%; SUVmax 3.65 [2.1-5.4]) and 12 (52.2%; SUVmax 3.75 [2.7-7.8]) patients, at 1st and 2nd evaluation respectively. All but one patient had received steroids at IRF diagnosis and 21 (91.3%) were in complete remission at both 1st and 2nd evaluation. During a median follow-up period of 38.7 [3-106.9] months, 6 (26.1%) patients suffered IRF relapse that occurred 15.7 [9.2-42.8] months after diagnosis. Multivariate analysis showed that only persistent retroperitoneal fibrosis FDG uptake at 2nd evaluation was associated with IRF relapse (p = .046). Conclusions: In IRF, persistent retroperitoneal fibrosis FDG uptake during follow up is associated with clinical outcome. FDG/PET CT may help to better stratify the risk of relapse and target therapy in IRF.

Patients with autoimmune hemolytic anemia (AIHA) may require intensive care unit (ICU) admission. In order to describe the characteristics of AIHA patients in ICU and identify prognosis factors, clinical and biological data from 44 patients admitted in one ICU between 2002 and 2015 were retrospectively analyzed. The main reasons for ICU admission were profound anemia without any organ failure in 19 patients (either for safer transfusion or continuous monitoring only). Twenty-five (57%) patients had a past history of hemopathy. Twenty patients presented with a direct anti-globulin test (DAT) positive for immunoglobulin G (DAT-IgG) only (46%), 8 with a DAT positive for both IgG and complement (DAT-IgG+C) (36%), and 16 with a DAT positive for complement only (DAT-IgG+C) (18%). Corticosteroids and rituximab were administered to respectively 44 (100%) and 12 (25%) patients. Red blood cell transfusion was required in 28 (64%) patients. Ten (23%) patients received vasopressors. Renal replacement therapy was necessary in 14 (31.8%) patients. Thirteen (30%) patients died in the ICU. There was no difference between survivors and non-survivors regarding associated comorbidities like hemopathy (18/31 [58%] vs. 7/13 [54%], p = 0.80). In decedents, age was higher (72 years [57.8–76.3] vs. 50 years [34.3–64], p < 0.01) and organ dysfunctions were more severe at day 1 (SOFA 8 [7–11] vs. 5.5 [3–7], p < 0.01). Patients with a DAT-IgG displayed poorer outcome in comparison with patients with DAT-IgG+C/C (hospital mortality 69% vs. 36%, p = 0.04). Mortality rate of AIHA patients requiring ICU admission is consequential and appears to be impacted by age, organ failures, and DAT-IgG.

Lichen planus (LP) remains often difficult-to-treat in its chronic, severe and erosive forms, requiring use of immunomodulatory (acitretin, PUVA, and extracorporeal photochemotherapy (EPC)) or off label immunosuppressive strategies (cyclosporine, azathioprine).1,2,3 However, the pathogenic role of an HPV-specific T-cell response in chronic LP, and the increased risk of neoplasia, especially in its severe mucosal forms, both support the use of T-cell-targeting immunosuppressants with antineoplastic attributes, such as mammalian target of rapamycin (mTOR) inhibitors4,5 . This article is protected by copyright. All rights reserved.