Characteristics and outcome of ANCA-associated vasculitides induced by anti-thyroid drugs: a multicentre retrospective case-control study.

OBJECTIVE: Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. METHODS: We performed a retrospective multicentre study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with four controls by gender and year of diagnosis. RESULTS: Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in six (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%) and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in seven (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in four (11%). ATD were reintroduced in seven cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs 25%, P = 0.007), but less frequent kidney (38 vs 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95% CI 0.01, 0.65, P = 0.019). CONCLUSION: ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

Characteristics of thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly syndrome: a retrospective study from a large Western cohort.

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.

Trans-bronchial lung cryobiopsy in patients at high-risk of complications.

BACKGROUND: The surgical lung biopsy (SLB) is the recommended sampling technique when the pathological analysis of the lung is required in the work-up of an interstitial lung disease (ILD) but trans-bronchial lung cryobiopsy (TBLC) is increasingly recognized as an alternative approach. As TBLCs have lower mortality and morbidity risks than SLB, this study aimed to investigate the safety of TBLCs in patients at higher risk of complications and for whom SLB was not considered as an alternative. METHOD: This prospective study was conducted in two hospitals in which TBLCs were performed in patients with body mass index (BMI) > 35, and/or older than 75 years, and/or with severely impaired lung function (FVC < 50% or DLCO < 30%), and/or systolic pulmonary artery pressure > 45 mmHg, and/or a clinically significant cardiac disease. Patients with any of these risk factors constituted the high-risk group. Clinical outcomes were compared with those obtained in patients without these risk factors (low-risk group). RESULTS: Ninety-six patients were included between April 2015 and April 2020, respectively 38 and 58 in the high-risk or the low-risk group. No statistically significant difference was observed between both groups in terms of severity and rate of bleeding, pneumothorax, or duration of hospital stay (p value ranging from 0.419 to 0.914). CONCLUSION: This preliminary study on a limited number of patients suggests that TBLC appears safe in those in whom lung biopsy is at high-risk of complications according to their age, BMI, lung impairment, and cardiac comorbidities.

Impact of hyponatremia on nerve conduction and muscle strength.

BACKGROUND: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies. DESIGN: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia. RESULTS: No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve). CONCLUSION: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia.

Efficacy of Low-Dose Tocilizumab on Relapsing Adult-Onset Still's Disease.

Still's disease is an inflammatory disorder of unknown etiology. First-line therapy is based on corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) but the frequency of relapses and corticosteroid-induced adverse events are limiting factors. The efficacy of intravenous tocilizumab (TCZ) has been shown at a dose of 8 mg/kg but the corticosteroid-sparing effect of intravenous low-dose TCZ followed by subcutaneous (SC) injection in the course of the disease has been poorly investigated. We report the case of a 28-year old Caucasian woman presenting a relapse of Still's disease eleven months after diagnosis under treatment with 6 mg of methylprednisolone. TCZ at a dose of 4 mg/kg every 2 weeks was combined with 32 mg of methylprednisolone, followed by 162 mg SC every 3 weeks. Evolution was rapidly favourable with a decrease in corticosteroid doses. We reviewed previously published cases.

Incidence and prognosis of dysnatraemia in critically ill patients: analysis of a large prevalence study.

BACKGROUND: The objective of this study is to assess the impact of dysnatraemia on mortality among intensive care unit (ICU) patients in a large, international cohort. MATERIAL AND METHODS: Analysis of the Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day (8 May 2007) worldwide multicenter, prospective point prevalence study. Hyponatraemia was categorized as mild (130-134 mM/L), moderate (125-129 mM/L) or severe (< 125 mM/L). Hypernatraemia was also categorized as mild (146-150 mM/L), moderate (151-155 mM/L) or severe (> 155 mM/L). Patients with normal serum sodium (135-145 mM/L) constituted the reference group. The main outcome was hospital mortality. Analysis was conducted separately for patients admitted on the study day (25.8%) and those already present on the ICU (74.2%). RESULTS: Serum sodium was measured in 13 276 of the 13 796 patients (96.2%). A total of 3815 patients (28.7%) had dysnatraemia: 12.9% with hyponatraemia and 15.8% with hypernatraemia. The prevalence of dysnatraemia was significantly greater in patients already present on the ICU prior to the study day than for those just admitted (13.1% vs. 12.3% for hyponatraemia and 17.1% vs. 12.1% for hypernatraemia, both P < 0.001). Hospital mortality rates were higher in patients with dysnatraemia than in those with normal sodium levels and were directly related to the severity of hypo- and hypernatraemia. This association between dysnatraemia and mortality was similar in infected and noninfected patients (P = 0.061). CONCLUSIONS: Dysnatraemia is more frequent during the ICU stay than on the day of admission. Dysnatraemia in the ICU - even mild - is an independent predictor of increased hospital mortality.

Gastrocnemius Myositis Associated with Behçet's Syndrome.

Behçet's syndrome is a complex vasculitis involving vessels of all sizes. The typical clinical presentation consists of recurrent oral ulcers associated with genital ulcers, and/or intra-ocular inflammation and/or cutaneous lesions. It may also involve the joints, central nervous system, cardiovascular system and gastrointestinal tract. Muscle involvement associated with Behçet's syndrome has been rarely described. We here report two cases of muscular manifestations in the setting of Behçet's syndrome with specific gastrocnemius muscle involvement. LEARNING POINTS: Behçet's syndrome (BS) is a vasculitis involving vessels of all sizes with multi-organ involvement.Myositis is a rare manifestation in the setting of BS.Musculoskeletal symptoms should be investigated in patients with BS.

Segmental Arterial Mediolysis and its Mimickers: A Case Report and Review of the Literature.

This case report addresses segmental arterial mediolysis (SAM), a rare non-inflammatory vasculopathy. A 51-year-old man presented at the emergency department for epigastric and left upper quadrant pain. He had a history of arterial hypertension and had recently received methylprednisolone for knee pain. Blood tests revealed elevated C-reactive protein levels at 40 mg/l and lactate dehydrogenase levels at 496 IU/ml. Abdominal computerized tomography showed arterial thickening, arterial dilatations, and dissections of the splenic and renal arteries, leading to organ ischemia. This case emphasizes the importance of considering SAM in cases of unexplained abdominal pain or suspected arteriopathy. LEARNING POINTS: Segmental arterial mediolysis (SAM) is a rare and underdiagnosed vasculopathy.SAM is a challenging diagnosis and should not be confused with vasculitis.SAM has a good prognosis with spontaneous resolution in most cases.

COVID-19 impact on an oncologic emergency department visits: observational study.

OBJECTIVE: This study aimed at evaluating the impact of COVID-19 on emergency department (ED) visits in a tertiary cancer centre and providing information on the features of the unplanned events during the first wave of COVID-19 pandemic. METHODS: This retrospective observational study based on data from ED reports was divided into three periods of 2 months each around the first lockdown announcement of 17 March 2020: pre-lockdown, lockdown and post-lockdown. RESULTS: A total of 903 ED visits were included in the analyses. The mean (±SD) daily number of ED visits did not change during the lockdown period (14.6±5.5) when compared with the periods before (13.6±4.5) and after lockdown (13.7±4.4) (p=0.78). The proportion of ED visits for fever and respiratory disorders increased significantly to 29.5% and 28.5%, respectively (p<0.01) during lockdown. Pain, the third most frequent motive, remained stable with 18.2% (p=0.83) throughout the three periods. Symptom severity also showed no significant differences in the three periods (p=0.31). CONCLUSION: Our study shows that ED visits during the first wave of the COVID-19 pandemic remained stable for our patients regardless of the symptom's severity. The fear of an in-hospital viral contamination appears weaker than the need for pain management or for the treatment of cancer-related complications. This study highlights the positive impact of cancer ED in the first-line treatment and supportive care of patients with cancer.

Giant cell arteritis with adventitial pattern in a 51-year-old man: A case report.

Clinical presentation as well as histological or biological findings can sometimes make the diagnosis of giant cell arteritis difficult. Histopathological features of temporal artery biopsy from giant cell arteritis patients are also challenging because of the various described appearances or even finding of clinically normal temporal artery biopsy does not rule out the diagnosis. We here describe the case of a 51-year-old man with temporal artery biopsy showing lymphocytes infiltrates in the adventitia corresponding to the so-called adventitial pattern of giant cell arteritis according to Hernandez-Rodriguez et al.

Lack of responsiveness to 1-desamino-D arginin vasopressin (desmopressin) in male patients with nephrogenic syndrome of inappropriate antidiuresis: from bench to bedside.

BACKGROUND: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described entity, linked to gain-of-function mutations (R137C and R137L) in arginine vasopressin (AVP) gene leading to chronic activation of tubular V2 AVP receptor (V2R) and thus free water reabsorption. In addition to collecting duct cells, the V2R is also expressed in endothelial cells, where it mediates the rise in circulating levels of von Willebrand factor (vWF) and coagulation factor VIII (fVIII). Recent in vitro data showed that these mutant receptors are resistant to vasopressin-stimulated cAMP production. We aimed to explore by clinical observations the sensitivity to vasopressin of the R137C-V2R mutant in vivo. MATERIAL AND METHODS: We performed a stimulation test with 1-desamino-D arginin vasopressin (dDAVP) 0·3 µg/kg of bodyweight in three patients (two hemizygous male and one heterozygous female) with NSIAD with R137C mutation and measured on the one hand the levels of vWF and fVIII and the other hand urine osmolality and albumin excretion (UAE). RESULTS: Whereas the female heterozygous patient displayed normal response to simulation by dDAVP (except for UAE), no increase in vWF, fVIII, urinary osmolality and UAE was observed among hemizygous male patients. CONCLUSIONS: Coherent with in vitro observation in transfected cells, our clinical observations demonstrate that the R137C-V2R mutant is resistant to vasopressin stimulation in its physiological sites of expression.

Recurrent 'Occult' 18F-FDG Uptake in an Atypical Case of Anti-Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

A 72-year-old woman, with anti-myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presented with two episodes of spinal pachymeningitis (at two different levels 9 years apart, cervical in 2011 and dorso-lumbar in 2020) associated with aortitis and only demonstrated by F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This association between aortitis and pachymeningitis in AAV appears exceptional. Moreover, the relapse of aortitis and pachymeningitis in 2020 was not accompanied by an increase in ANCA. This case demonstrates the value of 18F-FDG PET/CT in the management of AAV, providing evidence of the recurrence and distribution of lesions in various organs, including those with unexpected involvement. LEARNING POINTS: Involvement of large vessels such as the aorta is rarely associated with anti-myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but has been described in a few cases. Possible aortic involvement should always be kept in mind while managing a patient with AAV.Pachymeningitis is rarely associated with AAV, but in case of unexplained and unspecific neurological symptoms in patients with AAV, such involvement should be considered.18F-FDG PET/CT is a promising tool for the management of patients with AAV, allowing unexpected sites, undetected by usual examinations, to be highlighted. In contrast to giant-cell arteritis, this exam has not, until now, been included in the recommended/systematic work-up of AAV.

Genetic testing in autoinflammatory diseases - past, current and future perspectives.

INTRODUCTION: Autoinflammatory diseases (AID) are a group of rare monogenic illnesses, leading to uncontrolled activation of the innate immune system and presenting with recurrent flares of systemic and localized inflammation. Diagnosis is confirmed by the detection of a class IV or class V gene variant in an AID-related gene and improvements in sequencing techniques have enabled the discovery of new entities. The aim of our study is to explore the diagnostic yield of evolving genetic testing methods for AID and to determine whether increasing gene panels generate a higher diagnostic rate. METHODS: Retrospective study of 2620 patients that underwent sequencing for a clinical suspicion of AID in Belgium, between January 2015 and December 2020. Sequencing was performed through a 10-gene panel between 2015 and 2017, a 25-gene panel between 2018 and 2020 and mendeliome technology with a 66- and a 502- in silico gene panel in 2020. RESULTS: The rate of genetic diagnoses increased along with the expansion of the gene panel with a diagnostic yield of 15% with 10 genes, 16% with 25 genes and 23% with 502 genes. CONCLUSION: Our study is the first nationwide study for autoinflammatory genetic testing and the first use of mendeliome technology for AID diagnosis. Although we confirmed that the bigger the gene panel, the higher the diagnostic rate, this technology generated inevitably a higher financial and human cost although the majority of diagnoses remained amongst the four original hereditary recurrent fevers (HRFs).