A case of VEXAS with microcytic anemia: don't be mislead by an associated condition!

BACKGROUND: VEXAS syndrome encompasses a wide range of rheumatological and hematological manifestations, which often features myelodysplastic syndrome accompanied by either macrocytic anemia or macrocytosis. CASE REPORT: A 61-year-old Sicilian male was referred for a microcytic anemia associated with skin lesions, recurrent fever, involuntary weight loss, recurrent superficial venous thrombosis, migratory polyarthritis and a lung nodule. A hemoglobin electrophoresis uncovered a minor beta-thalassemia contributing to the anemia in addition to the chronic inflammation and vitamin B9/B12 deficiencies. A bone marrow aspiration demonstrated the presence of vacuoles in erythroid and myeloid precursors, as well as dysplasia in all three lineages. This led us to consider VEXAS syndrome which was confirmed by the presence of UBA1 mutation type p.M41T. Low-dose steroids and sarilumab (200 mg every 3 weeks) therapy led to a transient partial remission. CONCLUSION: The pivotal insight from this observation centers around the microcytic characteristic of the anemia, with the confounding factor being minor thalassemia, whereas the type of anemia typically associated with VEXAS is macrocytic. This finding may be of particular relevance to patients from regions with endemic thalassemia. Consequently, the presence of microcytic anemia should not hinder clinicians from considering VEXAS syndrome in the appropriate clinical context.

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.

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.

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.

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.

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.

Isolated adrenocorticotropic hormone deficiency and sialadenitis associated with nivolumab: a case report.

BACKGROUND: Immune checkpoint inhibition with anti-PD(L)1 and anti-CTLA4 antibodies has significantly changed cancer treatment during the last 10 years. Nevertheless, boosting the immune system with immune checkpoint inhibition can result in immune-related adverse events, affecting different organ systems, among which the endocrine system is the most affected. However, there are few descriptions of the association of immune-related adverse events, and the pathophysiology of some is still lacking. Here, we report a 70-year-old Caucasian patient treated with nivolumab (anti-PD1 monoclonal antibody) after resection of a unique relapse of melanoma in the neck region who presented with sicca syndrome, extreme fatigue, and weight loss 6 months after the start of anti-PD1 therapy. Blood tests revealed hypoglycemia and secondary hypocortisolism due to isolated adrenocorticotrophic hormone deficiency. Interestingly, brain methionine positron emission tomography/magnetic resonance revealed physiological metabolism of the pituitary gland, which was not increased in size, and no hypophyseal metastasis was detected. The sicca syndrome investigation revealed the absence of anti-SSA/SSB antibodies, while the labial salivary gland biopsy showed lymphoplasmatocytic infiltrates with a focus score of 1. To provide new insights into the physiopathology of the anti-PD1-related sialadenitis, we investigated the distribution of aquaporins 5 by immunostaining on the labial salivary gland acini, and compared this distribution with the one expressed in the primary Sjögren's syndrome. Contrary to patients with primary Sjögren's syndrome (in whom aquaporins 5 is mainly expressed at the basolateral side), but similar to the patients with no sialadenitis, we observed expression of aquaporins 5 at the apical pole. This new finding deserves to be confirmed in other patients with anti-PD1-related sialadenitis. Owing to these immune-related adverse events, anti-PD1 was stopped; nevertheless, the patient developed a new relapse 1 year later (March 2020) in the neck region, which was treated by radiotherapy. Since then, no relapse of melanoma was seen (1.5 years after radiotherapy), but the patient still requires hypophyseal replacement therapy. The sialoadenitis resolved partially. CONCLUSION: We report a combination of sialoadenitis and hypophysitis explaining extreme fatigue in a patient who was treated in the adjuvant setting with anti-PD1 for a melanoma relapse.

Atypical acute disseminated encephalomyelitis with systemic inflammation after a first dose of AztraZaneca COVID-19 vaccine. A case report.

Background: Only a few cases of acute disseminated encephalomyelitis (ADEM) following coronavirus disease 19 (COVID-19) vaccination have been described since the beginning of the vaccination campaign. Results: Here we report the first case of central nervous system (CNS) demyelination with systemic inflammatory findings on whole body 19-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) following the ChAdOx1 nCoV-19 vaccine. Conclusions: Clinicians should stay aware of potential new adverse events after immunization.

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).

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.

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.

Sequential development of ANCA-associated vasculitis and anti-GBM disease: A report of two cases.

In case of AAV with kidney involvement, physicians should explore anti-GBM antibodies and be aware of the possible sequential development of AAV, especially with MPO-ANCA, and anti-GBM glomerulonephritis. This sequential disease history is associated with a poor renal outcome, highlighting the need for urgent diagnosis and management.

Intrinsic Capacity Assessment by a Mobile Geriatric Team During the Covid-19 Pandemic.

In the autumn of 2020, the second wave of the COVID-19 pandemic hit Europe. In this context, because of the insufficient number of beds in geriatric COVID units, non-geriatric wards were confronted with a significant number of admissions of geriatric patients. In this perspective article, we describe the role of a mobile geriatric team in the framework of the COVID-19 pandemic and specifically how it assisted other specialists in the management of hospitalized geriatric patients by implementing a new approach: the systematic assessment and optimization of Intrinsic Capacity functions. For each patient, assessed by this consultative team, an individualized care plan, including an anticipated end-of-life decision-making process, was established. Intensity of care was most often not stated by considering chronological age but rather the comorbidity burden, the frailty status, and the patient's wishes. Further studies are needed to determine if this mobile geriatric team approach was beneficial in terms of mortality, length of stay, or functional, psychological, and cognitive outcomes in COVID-19 geriatric 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.

A Rare Case of a Metastatic Malignant Abrikossoff Tumor.

Abrikossoff tumor, also called granular cell tumor (GCT), is a neoplasm of the soft tissues which is most commonly a solitary, painless, and benign tumor. However, 2% of Abrikossoff tumors can be malignant. We report here the case of a 75-year-old male who presented a local recurrence of Abrikossoff tumor of the left thigh. The anatomopathological analysis concluded to a malignant GCT, and the F-18 fluorodeoxyglucose positron emission tomography showed multiple lesions in the lymph nodes and bones. The potential conversion to malignancy should alert practitioners because of the extremely poor prognosis. The diagnosis of malignant granular cell tumor should be based on a bundle of clinical and histological features and not solely on histologic features because of the challenging distinction between malignant and benign tumors due to the lack of well-defined criteria for the diagnosis of malignancy. Large size and recurrence are the most important clinical features predicting malignant behavior. Patients with a history of Abrikossoff tumor should be followed closely to monitor recurrence and malignant transformation. The apparent originality of our observation - which could lie in the evolution of a GCT tumor, initially considered as benign, to a malignant form - has to be challenged regarding the issue of classifying some cases according to the classical "benign" and "malignant" dichotomy.

Hydroxychloroquine in a G6PD-Deficient Patient with COVID-19 Complicated by Haemolytic Anaemia: Culprit or Innocent Bystander?

Hydroxychloroquine has been used worldwide as a first-line treatment for patients hospitalized with COVID-19. Little is known about COVID-19 and its effects on patients with congenital red blood cell disorders. We report a case of haemolytic anaemia in a 32-year-old patient and a fortuitous highlighting of G6PD deficiency. We reviewed the literature to assess the risk of hydroxychloroquine use in this context. LEARNING POINTS: A rapid drop in haemoglobin in COVID-19 patients should alert physicians to test for haemolytic anaemia and enzymopathies.Our review of the literature shows that use of hydroxychloroquine is safe in G6PD-deficient patients.