Trabecular bone score (TBS) in Cushing's disease: TBS gain after hypercortisolism normalization.

CONTEXT: Hypercortisolism frequently induces trabecular bone loss, more pronounced at the lumbar spine, resulting in osteoporosis, and thus an increase in fracture risk. Several studies have shown bone mass recovery in patients with Cushing's disease (CD) after treatment. OBJECTIVE: To examine treatment effects on TBS (trabecular bone score) in addition to aBMD (areal bone mineral density) in a cohort of patients with CD. DESIGN AND SETTING: Single-center retrospective longitudinal study in patients diagnosed with CD and successfully treated following surgery and/or medical treatment. PATIENTS: We included 31 patients with median age and BMI (body mass index) of 37.7 [28.4;43.3] years old and 27.7 [25.8;30.4] kg/m2, respectively. Median 24 h urinary cortisol before treatment was 213.4 [168.5;478.5] µg/24 h. All subjects were completely biochemically controlled or cured after treatment. MAIN OUTCOME MEASURES: aBMD and TBS were evaluated at AP Spine (L1-L4) with DXA prodigy (GE-Lunar), QDR 4500 (Hologic), and TBS iNsight® (Med-Imaps) before and after treatment. RESULTS: Absolute TBS and aBMD gains following cure of CD were significant (p < 0.0001, and p < 0.001, respectively). aBMD and TBS increased by +3.9 and 8.2 % respectively after cure of CD. aBMD and TBS were not correlated before (p = 0.43) and after treatment (p = 0.53). Linear regression analyses showed that TBS gain was independent of baseline BMI and that low TBS at baseline was predictive of TBS gain after treatment. CONCLUSION: The more significant improvement of microarchitecture assessed by TBS than aBMD and the absence of correlation between TBS and aBMD suggest that TBS may be an adequate marker of bone restoration after cure of CD. To support this conclusion, future studies with larger sample sizes and longer follow-up periods should be carried out.

Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases.

BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.

Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

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.

Prevalence of cardiovascular risk factors, the use of statins and of aspirin in Takayasu Arteritis.

The aim of this study was to assess the prevalence of cardiovascular risk factors in TAK, to describe the use of aspirin and statins and the risk factors associated with vascular ischemic complications and relapses. We conducted a retrospective study on TAK patients diagnosed between 2010 and 2018. Demographic, clinical, laboratory data and treatments were evaluated at diagnosis and during the follow-up. We included fifty-two TAK patients with median age 37.5 years [range 16-53] and 43 (83%) women. At diagnosis, cardiovascular risk factors were present in 32 (62%) patients: hypertension (n = 20, 38%), hyperlipidemia (n = 8, 15%), tobacco use (n = 16, 31%). During the median 4-year follow-up [range 0.1-17 years], 17 (33%) patients had at least one ischemic event and 15 (29%) patients needed endovascular procedure. Whereas TAK patients with cardiovascular risk factors were more frequently on statins and anti-hypertensive drugs, they have higher rates of cumulative ischemic complications (5 (24%) versus 21 (67%); p = 0.004), but similar rates of aspirin-treated patients. Patients who have developed vascular ischemic events were more frequently smokers (53% versus 20%; p = 0.03). The vascular complication-free survival was not significantly different in TAK patients with or without statins or aspirin at diagnosis. During the follow-up, 27 (52%) patients had at least one relapse, and the relapse-free survival was not significantly different in patients treated with statins or aspirin. Cardiovascular risk factors in TAK have to be strictly controlled since these risk factors could be associated with increased risk of ischemic complications.

Giant-cell arteritis associated with myelodysplastic syndrome: French multicenter case control study and literature review.

INTRODUCTION: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN. PATIENTS AND METHODS: Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone. RESULTS: Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival. CONCLUSION: Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.