Abstract Radioembolization using 90Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons’ exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

Background: Integrating immunotherapy with locoregional therapies marks a significant milestone in the realm of hepatocellular carcinoma (HCC) treatment . This study aimed to assess the impact of addition of AtezolizumabBevacizumab (AtezoBev) on the outcome patients treated with SIRT. Methods: We conducted a study that included all Child-Pugh A HCC treated with SIRT since 2017. We examined the effects of the addition of 3 infusions of AtezoBev before the SIRT procedure and after SIRT on patients outcome (AtezoBev-SIRT group). Time-to-event data were analyzed using Kaplan-Meier with the log-rank test. Results: Thirty five HCC patients treated with SIRT were included, of whom 23 % also received AtezoBev infusions. The two groups were similar in terms of liver function and HCC parameters. The median OS was not reached for patients who received AtezoBev in combination with SIRT and 14 months for patients only treated by SIRT. The median PFS was higher in the group treated by SIRT and AtezoBev vs SIRT alone (11.3 months vs 5.8 months). In the global cohort, 8 patients presented a downstaging (23 %), 4 underwent liver surgery (1 in the AtezoBev-SIRT group) and 4 liver transplantation (1 in the AtezoBev-SIRT group) Conclusions: The administration of AtezoBev, both before and after SIRT, is associated with enhanced OS and PFS outcomes compared to SIRT alone for unresectable HCC.

In current guidelines, liver transplantation (LT) should be considered in patients with early-stage hepatocellular carcinoma (HCC) because of their lower risk of recurrence and excellent long-term overall survival (OS). To broaden curative opportunities in intermediate and advanced HCC, downstaging strategies are emerging and associated with similar OS compared to patients initially meeting LT criteria. These strategies may however expose these patients to higher HCC recurrence risk. HCC recurrence post LT is essentially metastatic and extrahepatic, and these patients’ prognosis is very poor. The treatments used in this case are tyrosine kinase inhibitors (TKIs) with a low response rate and bad tolerance. If immunotherapy is the new standard of care for advanced and metastatic HCC, scarce data about their administration in liver transplanted recipients in case of HCC recurrence are available. As immunosuppressive (IS) treatment and immunotherapy agents share common targets, utilization of immunotherapy in liver recipients remains complex and exposes patients to acute cellular rejection (ACR). We would like to share in this letter our center experience with eight patients that received immunotherapy post LT as long as a standardized specific IS regimen that aims to lower ACR risk and allow immunotherapy to be effective.

OBJECTIVES:Sarcoidosis is a multisystemic granulomatosis diagnosed mainly in young adults. 18F-fluorodeoxyglucose (18F-FDG) PET/CT is useful in sarcoidosis cases to search for a biopsiable site or assess disease activity.18F-FDG PET/CT can reveal bone hypermetabolism in sarcoidosis patients, even in the absence of osteoarticular symptoms. The aim of this study was to describe metabolic bone involvement in sarcoidosis patients and to evaluate its prognostic impact. METHODS:This was an observational, comparative, retrospective, monocentric study. Inclusion criteria were a confirmed diagnosis of sarcoidosis according to the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria and at least one 18F-FDG PET/CT scan during follow-up. Metabolic bone involvement of sarcoidosis was defined as focal bone hypermetabolism with no argument for a differential diagnosis of bone 18F-FDG uptake. Patients with and without bone involvement were compared. RESULTS:Among the 175 included patients, 32 (18%) had metabolic bone involvement of sarcoidosis. The metabolic bone involvement was mainly axial and mostly without bone abnormalities on CT. Metabolic bone involvement was associated with intrathoracic and extrathoracic lymph node involvement and with a greater number of organs involved. Patients with metabolic bone involvement more frequently received corticosteroids, methotrexate and TNF-α inhibitors and a greater number of treatments. Relapse of sarcoidosis occurred sooner in patients with metabolic bone involvement. CONCLUSION:These results suggest that metabolic bone involvement is associated with more diffuse and more severe sarcoidosis.

Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. A total of 205 patients with first BCR after radical prostatectomy (73

La radio-embolisation hépatique (REH) par microsphères marquées à l’Yttrium-90 (90Y) peut être pratiquée dans l’attente d’une greffe hépatique ou pour réduire le volume tumoral avant chirurgie. Les directives actuelles recommandent de différer les transplantations d’au moins 14 jours après une REH pour limiter l’exposition des chirurgiens. Quarante-huit heures après la réalisation d’une REH pour un carcinome hépatocellulaire (860 MBq d’90Y), un patient est pris en charge au bloc opératoire pour une greffe hépatique, puis transféré en réanimation, sans consigne de radioprotection ni suivi dosimétrique spécifique. Le service de médecine nucléaire et le service compétent en radioprotection sont informés après l’intervention chirurgicale et le transfert de la pièce opératoire au service d’anatomie et cytologie pathologiques (ACP). Les mesures réalisées immédiatement sur sites (bloc opératoire, réanimation et ACP) n’ont révélé aucune contamination résiduelle surfacique. L’exposition externe des professionnels intervenus dans la prise en charge du patient et du foie radio-embolisé (3 chirurgiens, un agent hospitalier et deux anatomopathologistes) a été estimée à partir des débits de dose mesurés au contact et à distance du foie explanté. Le débit de dose lors de la greffe a été estimé à 6 mSv/h au contact du foie, 0,6 mSv/h à 30 cm et 0,04 mSv/h à 1 mètre du foie. En considérant les conditions les plus défavorables, les personnels les plus exposés sont les chirurgiens, qui auraient reçu une dose de 2,4 mSv au corps entier et 24 mSv aux extrémités. Cet événement a fait l’objet d’une déclaration et a été classé au niveau 1 de l’échelle INES par l’ASN. Le personnel soignant peut-être exposé à des risques de contamination/exposition en cas de prise en charge chirurgicale précoce après REH. Les estimations de dose ont permis de définir, selon l’activité administrée, le délai minimal à respecter avant transplantation hépatique de façon à ne pas dépasser un tiers des limites de doses annuelles réglementaires au corps entier et aux extrémités. En considérant une exposition du chirurgien de 4H à une distance de 30 cm du foie radio-embolisé, nous préconisons désormais un délai entre la greffe et la REH de 1 à 9 jours pour une activité, respectivement, comprise entre 100 et 3000 MBq. Ce délai figure dans le compte rendu de REH. Il apparaît possible de réaliser une transplantation hépatique moins de 14 jours après une REH à condition que les consignes de radioprotection, le suivi dosimétrique des professionnels et la vérification de la non-contamination surfacique soient appliqués.

PURPOSE:Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS:This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS:A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS:The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Background Sarcoidosis is a multisystemic granulomatosis of unknown cause. Prevalence of bone sarcoidosis is estimated between 3 and 30%. Bone sarcoidosis is symptomatic in about half of the cases. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is a useful imaging modality in sarcoidosis, to search for a biopsiable site, evaluate organ involvement or assess disease activity. It is a sensitive imaging modality to detect bone involvement. However, clinical and prognostic significance of hypermetabolic bone involvement of sarcoidosis is not well known. Objectives The aim of this study was to compare the characteristics of patients with and without hypermetabolic bone involvement of sarcoidosis and to evaluate the impact of metabolic bone involvement on treatments and outcomes. Methods This was an observational, comparative, retrospective monocentric study of prospectively collected data. Inclusion criteria were a diagnosis of sarcoidosis according to the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) criteria and at least one 18F-FDG PET-CT during follow-up. Metabolic bone involvement of sarcoidosis was defined as bone hypermetabolism for which alternative causes had been reasonably excluded, following the WASOG criteria of « at least probable » bone sarcoidosis. Characteristics of patients with and without bone involvement were compared using bilateral Fisher or Mann-Whitney tests. Relapse-free survival curves were constructed following the Kaplan-Meier method and compared using a log-rank test. A p-value < 0.05 was considered significant. Results Among 503 patients with sarcoidosis, 165 with definite sarcoidosis who had undergone at least one 18F-FDG PET-CT were included. Fourteen patients had positive bone PET-CT findings which were attributed to other cause than sarcoidosis. Metabolic bone involvement of sarcoidosis was found in 29 patients (18%), among which 9 (31%) had structural bone lesions on CT. Metabolic bone involvement of sarcoidosis was associated with more frequent intrathoracic lymph node involvement (28 [96%] and 107 [79%], p < 0.001), extrathoracic lymph node involvement (15 [52%] and 40 [30%], p = 0.03) and a higher number of organ involvements (median [interquartile range], 6 [4-7] and 4 [2-5], p < 0.001). Patients with metabolic bone involvement received more frequently corticosteroids (29 [100%] and 99 [73%], p < 0.001), methotrexate (26 [90%] and 66 [48%], p < 0.001), tumor necrosis factor (TNF) alpha inhibitors (22 [76%] and 41 [30%], p < 0.001), and a higher number of treatments (3 [3-4] and 2 [1-3], p < 0.001). Despite more intensive treatments, disease relapse occurred significantly sooner in patients with metabolic bone involvement of sarcoidosis (median time to the first relapse, 63 [44-84] months and 96 [72-156] months respectively, p = 0.01). Conclusion Metabolic bone involvement on PET-CT was present in 18% of patients with sarcoidosis. It was predominantly axial and without structural lesions. In this comparative study, patients with metabolic bone involvement received significantly more treatments and had a shorter time to relapse. It could therefore reflect a more severe multisystemic involvement and chronic evolution of the disease. This could help adjust individual therapeutic strategy for patients with sarcoidosis. References [1]Challenges of Sarcoidosis and Its Management. Drent M, Crouser ED, Grunewald J. N Engl J Med. 2021 Sep 9;385(11):1018-1032. [2]Clinical Presentation and Treatment of High-Risk Sarcoidosis. Perlman DM, Sudheendra MT, Furuya Y, Shenoy C, Kalra R, Roukoz H, Markowitz J, Maier LA, Bhargava M. Ann Am Thorac Soc. 2021 Sep 15. doi: 10.1513/AnnalsATS.202102- 212CME Figure 1. Disclosure of Interests None declared

La sarcoïdose est une maladie granulomateuse multisystémique de cause inconnue. La prévalence de l'atteinte osseuse est estimée entre 3 et 30 %. Elle est symptomatique dans environ la moitié des cas. La tomographie par émission de positrons (TEP) au 18F-fluorodéoxyglucose (FDG) associée à la tomodensitométrie (TDM) est un examen fréquemment utilisé au cours de la sarcoïdose pour chercher une cible biopsiable, évaluer les atteintes cardiaques, évaluer l'activité des stades IV pulmonaires, ou chercher des signes d'activité. Elle est sensible pour détecter l'atteinte osseuse, mais la signification clinique et pronostique des hypermétabolismes osseux n'est pas connue. Il s'agissait d'une étude rétrospective monocentrique de données collectées prospectivement. Les critères d'inclusion étaient une sarcoïdose définie selon les critères WASOG, comportant une documentation histologique, et la réalisation d'au moins une TEP-TDM au cours du suivi. Les atteintes osseuses métaboliques remplissant les critères WASOG d'atteinte « au moins probable » ou « hautement probable » ont été retenues. Les caractéristiques des patients avec et sans atteinte osseuse métabolique de la sarcoïdose ont été comparés avec un test de Fisher. Des courbes de survie sans rechute ont été construites par la méthode de Kaplan–Meier et comparées avec un test du log-rank. Une valeur p < 0,05 a été considéré significative. Parmi 503 patients ayant une sarcoïdose, 165 patients atteints de sarcoïdose définie ayant passé au moins une TEP-TDM ont été inclus. Quatorze patients présentaient un hypermétabolisme osseux d'autre cause que la sarcoïdose. Une atteinte osseuse métabolique de la sarcoïdose a été mise en évidence chez 29 patients (18 %), dont 9 (31 %) présentaient une atteinte osseuse structurale au scanner. L'atteinte osseuse métabolique de la sarcoïdose était associée à une atteinte ganglionnaire intrathoracique (28 [96 %] et 107 [79 %], p < 0,001) et extrathoracique (15 [52 %] et 40 [30 %], p = 0,03) plus fréquente. Les patients avec une atteinte osseuse métabolique recevaient plus fréquemment un traitement par corticoïdes (29 [100 %] et 99 [73 %], p < 0,001), méthotrexate (26 [90 %] et 66 [48 %], p < 0,001) et anti-tumor necrosis factor (TNF) alpha (22 [76 %] et 41 [30 %], p < 0,001). Malgré des traitements plus agressifs, la rechute survenait significativement plus tôt chez les patients avec une atteinte osseuse métabolique (délai médian à la première rechute, 63 [44–84] mois et 96 [72–156] mois respectivement, p = 0,01). L'atteinte osseuse métabolique de la sarcoïdose est présente chez 18 % des patients. Elle est le plus souvent axiale et sans lésion structurale sous-jacente. Dans cette étude comparative, elle est associée à des traitements plus fréquents et des rechutes plus précoces, représentant ainsi un signe de sévérité et de chronicité de la maladie. Cette donnée pourrait permettre d'ajuster la stratégie thérapeutique individuelle des patients atteints de sarcoïdose.

Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (<100 G/L) after exclusion of other causes. Mostly primary, it is associated with hematological malignancy, autoimmune disorders, or infection in 20% of patients. It is exceptionally described in patients with histiocytosis, mostly in children (seven patients in literature). We report a case of a 69-year-old man with ITP leading to the diagnosis of histiocytosis. At ITP's diagnosis, the patient had elevated gamma-globulins leading to computed tomography showing bilateral peri-renal infiltration. The biopsy showed enriched IgG-4 peri-renal Rosai Dorfman disease with MAP2K1 mutation, although peri-renal infiltration is highly suggestive of Erdheim-Chester disease. This overlapping association was described in men with mutation in MAP2K1 gene. Macrophages are implicated in the pathophysiology of ITP in multiple ways, notably by the phagocytosis of opsonized platelets and their function of antigen-presenting cells able to stimulate autoreactive T cells. Histiocytic cells derivate from monocyte-macrophage lineage. Activation of macrophages in active histiocytosis is responsible for consequential platelet destruction in ITP associated histiocytosis. Finally, this case highlights a rare presentation of ITP revealing histiocytosis, both being efficiently treated with rituximab.

Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Objective CNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies. Methods This was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III. Results Ninety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the BRAFV600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, p = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%. Conclusions CNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular. Classification of evidence This study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.

BACKGROUND: Destombes-Rosai-Dorfman disease (RDD) is a rare multisystemic histiocytosis. Pulmonary involvement during RDD has been poorly described. The goal of this study was to examine the clinical presentations, radiological features, and outcomes of 15 patients with RDD and lung involvement. METHODS: The cases of RDD with lung involvement were extracted from the French National Histiocytosis registry. Efficacy of the MEK inhibitor cobimetinib in treating lung disease was evaluated with an (18)fluorodeoxyglucose PET scanner and chest CT scans. RESULTS: Fifteen patients (six women; median age, 40 years at RDD diagnosis) were included. All patients had evidence of systemic disease with extrapulmonary localizations of the disease (lymphadenopathy [n = 12], skin [n = 9], bones [n = 6], retroperitoneal involvement [n = 3], sinuses [n = 3], parotid gland [n = 2], submandibular gland [n = 1], and breast [n = 1]). Presenting symptoms were dominated by dyspnea and dry cough in seven patients. Restrictive physiology was observed in two of five patients. BAL showed lymphocytosis in one of five cases. Eight patients received corticosteroids, all but one with variable immunosuppressive or immunomodulatory therapies. Two patients received cobimetinib for severe lung disease, with dramatic pulmonary metabolic and tumoral responses. Two patients died during follow-up: one of hemoptysis, and the other of an unrelated cerebral tumor. CONCLUSIONS: Pulmonary involvement in RDD is rare, proteiform, and sometimes severe. The MEK inhibitor cobimetinib can lead to dramatic responses.

BackgroundCardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown.MethodsAll French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared.ResultsFifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy.ConclusionCS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques.

Les histiocytoses sont un groupe hétérogène de maladies caractérisées par l’accumulation d’histiocytes dans des organes variés. La mise en évidence d’anomalies moléculaires somatiques dans certaines d’entre elles a conduit à une nouvelle classification. Nous détaillons dans cette revue les atteintes osseuses des histiocytoses du groupe L (histiocytose Langerhansienne (HL) et maladie d’Erdheim-Chester (MEC)) et de la maladie de Destombes-Rosai-Dorfman (DRD). Les atteintes osseuses de l’HL sont constituées essentiellement d’atteintes lytiques, uni ou multifocales, hypermétaboliques sur la scintigraphie ou la tomodensitométrie par émission de positons (TEP) au 18 fluorodéoxyglucose (FDG), touchant principalement les os plats et les vertèbres et plus rarement les membres, avec un risque fracturaire. La MEC est caractérisée par une atteinte métaphyso-diaphysaire des os longs, présente dans plus de 90 % des cas, et constituant une atteinte iconique de la maladie. Les douleurs osseuses peuvent être révélatrices de la MEC. La maladie de DRD est caractérisée par une atteinte osseuse multifocale des membres ou du rachis, associée dans les formes typiques à des atteintes ganglionnaires. Les traitements diffèrent dans ces 3 types d’histiocytoses et vont d’une abstention thérapeutique à des chimiothérapies dans l’HL, de traitements immunomodulateurs à des thérapies ciblées dans la MEC et d’une corticothérapie à des chimiothérapies dans la maladie de DRD.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by long bones and various other organs’ involvements.1 Tissues are infiltrated by CD68+ CD1a− foamy histiocytes.2 Therapeutic options are pegylated interferon-α,3 cladribine,4 mTOR inhibitors5 and anakinra in mild forms of ECD.6 7 Conversely, targeted BRAF or MEK inhibitor therapies are used for refractory or life-threatening ECD manifestations.8 9 All these therapies have frequent side effects. Interferon-α leads to fatigue, cytopenias and autoimmune diseases. Anakinra needs subcutaneous daily injections, with frequent local intolerance. Targeted therapies cause skin cancers, QT allongement, rhabdomyolysis and haemorrhage,10 and we lack long-term safety data with these drugs. Moreover, targeted therapies are not available in all countries. Thus, there is an unmet need for improving treatments in many patients with ECD, particularly in countries where access to targeted therapies is complicated or impossible. Although our comprehension of this disease has recently moved from inflammatory to clonal myeloproliferative disease,11 the accumulation of pathological histiocytes leads to an increase of several cytokines in blood and affected tissues. Cytokine/chemokine network has been described in ECD lesions, and most of these factors are regulated by tumour necrosis factor alpha (TNF-α), which is also expressed in ECD lesions and serous fluids like pericardial effusion12–14 and has been implicated in ECD pathogenesis in in vitro models.15 Two ECD patients with cardiovascular involvement were successfully treated with infliximab, a TNF-α monoclonal chimeric antibody, achieving an improvement of symptoms, cardiac involvement and function.14 We aim to determine the efficacy of infliximab in a larger series of patients with ECD. We retrospectively reviewed …