Co-occurrence of Dermatomyositis and Polycythemia Unveiling Rare de Novo Neuroendocrine Prostate Tumor

We present a case of dermatomyositis together with polycythemia as initial manifestations of a particularly rare type of prostate cancer. A 69-year-old man was hospitalized for facial erythema and symptoms of fatigue. Physical evaluation, serum creatinine phosphokinase and electromyography were consistent with dermatomyositis. In parallel, the hemoglobin level was 18.5 g/dL, serum erythropoietin levels were low normal and no JAK2 mutation was found. Given a strong suspicion of a paraneoplastic syndrome the patient underwent abdominal computed tomography revealing a prostate mass, enlarged iliac lymph nodes and a fracture of L1 due to metastasis. The unusual paraneoplastic manifestations prompted a more thorough immunohistologic examination of the needle biopsy specimen taken from the prostate, which led to the diagnosis of large cell neuroendocrine prostate carcinoma. It is a most rare type of prostate cancer, carrying a poor prognosis. To our knowledge, this is the first case in the literature associating a neuroendocrine cancer of the prostate with dermatomyositis

Obstetric Outcomes in Women with Rheumatic Disease and COVID-19 in the Context of Vaccination Status

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi -square or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2%(n = 2). CONCLUSION: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy

Cardiovascular risk in patients with spondyloarthropathies

The spondyloarthritides, particularly ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have been related to an increased cardiovascular morbidity and mortality. The purpose of the study was to investigate whether spondyloarthritis patients have an increased prevalence of cardiovascular risk factors and the role of inflammation in disturbing them. In a cross-sectional study, non-diabetic patients with spondyloarthritis were compared to age- and sex-matched apparently healthy control subjects as regards classic cardiovascular risk factors. It was demonstrated that patients were significantly more often smokers, had lower high density lipoprotein (HDL) cholesterol levels and an elevated atherogenic index (total cholesterol/HDL). After adjustment for smoking, patients still had lower HDL values. Furthermore, PsA patients had a higher waist-to-hip ratio (WHR, an index of abdominal obesity) and serum urate levels than controls, while they more often fulfilled the criteria for the metabolic syndrome. In univariate analysis, laboratory markers of inflammation were significantly negatively correlated with HDL and apolipoprotein (Apo) AI levels, whereas, particularly in PsA, there was an additional positive correlation between inflammatory markers and obesity measures (body mass index, WHR), as well as the atherogenic index. Spondyloarthritis patients had a significantly increased carotid intima-media thickness compared to controls, although this ceased to be significant after adjustment for smoking. A group of patients with active spondyloarthritis who had not been on immunomodulatory treatment were followed for up to one year after treatment initiation. Although treatment with TNFα inhibitors and/or synthetic disease-modifying antirheumatic drugs (and low-dose glucocorticoids in 3 patients) produced a significant improvement in laboratory and clinical measures of disease activity both at 6 and 12 months, there was no significant change in either the obesity measures or serum lipid levels. It was only at 6 months that a significant decline in ApoB levels was noted coupled with a small borderline improvement in ApoAI levels and the ApoB/ApoAI ratio. However, these alterations were not sustained up to 12 months. In conclusion, spondyloarthritis patients have an increased prevalence of classic cardiovascular risk factors (smoking, low HDL and in PsA abdominal obesity and metabolic syndrome). Inflammation appears to adversely affect these factors. Immunomodulatory treatment does not seem to substantially modify obesity measures or the lipid profile, although its influence on actual cardiovascular event rates remains unknown.Οι σπονδυλαρθρίτιδες, και κυρίως η αγκυλοποιητική σπονδυλίτιδα (ΑΣ) και η ψωριασική αρθρίτιδα (ΨΑ), έχουν συνδεθεί με αυξημένη καρδιαγγειακή νοσηρότητα και θνησιμότητα. Ο σκοπός της μελέτης ήταν να διερευνήσουμε αν οι ασθενείς με σπονδυλαρθρίτιδα έχουν αυξημένο επιπολασμό παραγόντων καρδιαγγειακού κινδύνου και το ρόλο της φλεγμονής στους παράγοντες αυτούς. Σε μια συγχρονική μελέτη, συγκρίναμε μη-διαβητικούς ασθενείς με σπονδυλαρθρίτιδα με φαινομενικά υγιή άτομα παρόμοιας ηλικίας και φύλου ως προς τους κλασικούς παράγοντες καρδιαγγειακού κινδύνου. Διαπιστώθηκε ότι οι ασθενείς ήταν στατιστικά συχνότερα καπνιστές, είχαν χαμηλότερα επίπεδα χοληστερόλης υψηλής πυκνότητας λιποπρωτεΐνης (HDL) και αυξημένο αθηρωματικό δείκτη (ολική χοληστερόλη/HDL). Μετά εξουδετέρωση της επίδρασης του καπνίσματος, οι ασθενείς εξακολουθούσαν να έχουν χαμηλότερες τιμές HDL. Επίσης, οι ασθενείς με ΨΑ είχαν υψηλότερο δείκτη κοιλιακής παχυσαρκίας και επίπεδα ουρικού οξέος από τους μάρτυρες και πληρούσαν συχνότερα τα κριτήρια για το μεταβολικό σύνδρομο. Σε μονοπαραγοντική ανάλυση, οι εργαστηριακοί δείκτες φλεγμονής είχαν μια στατιστικώς αντίστροφη συσχέτιση με τα επίπεδα HDL και απολιποπρωτεΐνης (Apo) ΑΙ του ορού, ενώ ειδικά στους ασθενείς με ΨΑ υπήρχε επιπλέον μια θετική συσχέτιση μεταξύ των δεικτών φλεγμονής και του αθηρωματικού δείκτη, καθώς και των δεικτών θρέψης (δείκτη μάζας σώματος, λόγου περιμέτρου μέσης προς ισχία). Οι ασθενείς με σπονδυλαρθρίτιδα είχαν σημαντικά αυξημένο πάχος έσω και μέσου χιτώνα των καρωτίδων σε σχέση με τους μάρτυρες, αν και η διαφορά αυτή έπαυε να είναι στατιστικώς σημαντική μετά προσαρμογή για το κάπνισμα. Μια ομάδα ασθενών με ενεργό σπονδυλαρθρίτιδα για την οποία δε λάμβαναν ανοσοτροποποιητική αγωγή παρακολουθήθηκαν για ένα έτος μετά την έναρξη της θεραπείας. Παρότι η θεραπεία με αντι-TNFα παράγοντες ή/και συνθετικά τροποποποιητικά της νόσου φάρμακα (και χαμηλές δόσεις γλυκοκορτικοειδών σε 3 ασθενείς) επέφερε μια σημαντική βελτίωση των εργαστηριακών και των κλινικών δεικτών ενεργότητας της νόσου τόσο στους 6, όσο και στους 12 μήνες, δεν υπήρξε καμία μεταβολή στους δείκτες θρέψης ή στα λιπίδια του ορού. Μόνο στους 6 μήνες διαπιστώθηκε μια σημαντική πτώση της ApoB και μια μικρή οριακά σημαντική βελτίωση της ApoAI και του κλάσματος ApoB/ApoAI. Ωστόσο, οι μεταβολές αυτές δε διατηρήθηκαν στους 12 μήνες. Συμπερασματικά, οι ασθενείς με σπονδυλαρθρίτιδα έχουν αυξημένο επιπολασμό κλασικών παραγόντων καρδιαγγειακού κινδύνου (κάπνισμα, χαμηλή HDL, ειδικά οι ασθενείς με ΨΑ κοιλιακή παχυσαρκία και μεταβολικό σύνδρομο). Η φλεγμονή δείχνει πως ενέχεται στη διατάραξη των παραγόντων αυτών. Η θεραπεία με ανοσοτροποποιητικά φάρμακα, δε φαίνεται να τροποποιεί ουσιαστικά τους δείκτες θρέψης ή το λιπιδικο προφίλ, αν και η επίδρασή της στα πραγματικά καρδιαγγειακά συμβάματα παραμένει άγνωστη

Periocular xanthogranuloma: A forgotten entity?

Charalampos Papagoras1, George Kitsos2, Paraskevi V Voulgari1, Anastasia K Zikou3, Maria I Argyropoulou3, Aikaterini Zioga4, Alexandros A Drosos11Rheumatology Clinic, Department of Internal Medicine; 2Department of Ophthalmology; 3Department of Clinical Imaging and Radiology, 4Department of Pathology, Medical School, University of Ioannina, Ioannina, GreeceAbstract: Periocular xanthogranulomatous diseases are a rare group of disorders which are characterized by a predilection to affect the orbit and ocular adnexa and special histopathological features, in particular infiltrates comprising non-Langerhans-derived foamy histiocytes and Touton giant cells. The differential diagnosis is difficult and occasionally definite diagnosis cannot be established even after clinical and histopathological findings are taken together. We describe a case of a middle-aged man who presented with a 10-year history of voluminous eyelid swelling with concomitant late-onset atopic manifestations, namely bronchial asthma and allergic rhinitis with nasal polyps. After thorough clinical and laboratory investigation, including a biopsy of the eyelid, we classified the patient’s disease to a rare entity that has been relatively recently described: periocular xanthogranuloma associated with adult-onset asthma. In a review of the literature, no prospective trials concerning the treatment of this disease were found. The literature mainly contained case reports and case series in which corticosteroids and chemotherapy with alkylating agents have been reported to be beneficial. We treated our patient with a combination of oral corticosteroids and cyclophosphamide pulses and we observed substantial regression of the eyelid masses together with a normalization of systemic immunologic abnormalities.Keywords: periocular xanthogranuloma, adult-onset asthma, non-Langerhans histiocytoses, cyclophosphamide, methylprednisolon

Counting Costs under Severe Financial Constraints: A Cost-of-Illness Analysis of Spondyloarthropathies in a Tertiary Hospital in Greece

Objective. To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece. Methods. Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros. Results. The mean +/- SD annual direct cost for the patients with SpA reached (sic)8680 +/- 6627. For the patients with PsA and AS, the cost was estimated to be (sic)8097 +/- 6802 and (sic)9531 +/- 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA. Conclusion. SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments

Serum granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in patients with active radiographic axial spondyloarthritis and persists despite anti-TNF treatment

$\bf Background:$ Accumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment. $\bf Methods:$ Patients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4–6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1). $\bf Results:$ Twelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3$\pm$2 and ASDAS 3.2$\pm$0.7, which decreased to 4.1$\pm$1.7 and 2.2$\pm$0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, $\it p$=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, $\it p$=0.001), but similar levels of SOST (369 vs 544pg/ml, $\it p$=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline ($\it r$=0.61, $\it p$=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other. $\bf Conclusions:$ GM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA

SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

International audienc