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Background: Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH., Methods: This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children's Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival., Findings: Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 vs. 26%, p  < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 vs. 79%, p  = 0.014), central nervous system (51  vs. 34%, p  = 0.007), facial/orbit (52 vs. 38%, p  = 0.031), lungs (43 vs. 28%, p  = 0.009), hypothalamic/pituitary axis (51 vs. 26%, p  < 0.001), skin (61 vs. 29%, p  < 0.001), and lymph nodes (15 vs. 7%, p  = 0.028); the BRAF V600E mutation was also more frequent in mixed ECD-LCH (81 vs. 59%, p  < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 vs. 29%, p  < 0.001) or as any line (75 vs. 24%, p  < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank p  = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432)., Interpretation: Mixed ECD-LCH is a multisystem disease driven by the BRAF V600E mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH., Funding: None., Competing Interests: AI reports research grants from Transgene, Sanofi, and Nutritheragene; consulting fees from Novocure, LeoPharma, Polytone Laser, and Novartis; honoraria from Novocure and Neurologies; travel funding from LeoPharma, Novocure, and Carthera. BT report consulting fees and honoraria from GSK, AstraZeneca, CSL Vifor, Boehringer Ingelheim, and Novartis; advisory board activity for Amgen., (© 2024 The Author(s).)

Objectives: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases., Methods: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019., Results: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10). Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years). Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued., Conclusion: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs., Competing Interests: Competing interests: XM received consulting fees from BMS, Novartis, Sanofi, Pfizer, UCB, Janssen, GSK, Galapagos and BMS and is RMD Open associate editor. JE-G received grants from BMS, Lilly, Pfizer (payments made to University of Strasbourg Foundation; no access to TATA data) and consulting fees from BMS, Galapagos, Abbvie, Janssen, Novartis, Pfizer, Sanofi, Gilead, Roche, Chugai and Lilly., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Introduction: Cocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed., Case Report: A 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made., Conclusion: CIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objectives: Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD., Methods: CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016., Results: 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3., Conclusions: Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.

Introduction: Pulmonary lesions may be a presenting feature of AL amyloidosis., Observation: We report a 49-year-old male with AL amyloidosis secondary to a multiple myeloma with symptomatic interstitial pulmonary lesions and chronic cough as the presenting feature., Conclusion: Lung involvement is relatively frequent during AL amyloidosis but most of the time it remains asymptomatic. Interstitial pneumonia is the rarest condition of pulmonary amyloidosis. It is related to a large diffusion of the disease as demonstrated by the usual concurrent presence of cardiac lesions., (Copyright © 2015. Published by Elsevier SAS.)

Competing Interests: G. Baulier déclare avoir été pris en charge en avril 2015 par Shire à l’occasion d’un déplacement à Amsterdam à l’occasion du Gaucher Expert Summit.