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A letter to the editor is presented about the complication of systemic lupus erythematosus with aortitis.

Evidence suggests that the symptom duration may affect the occurrence of certain fever (FUO) and inflammation (IUO) of unknown origin associated conditions. It is unclear if this could potentially guide diagnostic evaluations. We examined the association between symptom duration and diagnostic and prognostic outcomes in FUO/IUO. We retrospectively analyzed a cohort of adult patients meeting criteria for FUO/IUO from a tertiary care center in Belgium between 2000 and 2019. The association between symptom duration and outcomes of interest were estimated by Cox proportional hazards models. Among 602 patients who met criteria for FUO/IUO (mean age 54 years, 43% female), 132 (22%) and 68 (11%) had symptoms for 3–12 months and >12 months, respectively. There were no significant differences in diagnosis or all-cause mortality between a symptom duration of <3 months and 3–12 months. In contrast, those who had a symptom duration of >12 months were less likely to receive a final diagnosis (aHR 0.42, 95% CI 0.30–0.60), in particular a diagnosis of infectious disorders (aHR 0.29, 95% CI 0.12–0.74), malignancies (aHR 0.11, 95% CI 0.03–0.46), and miscellaneous conditions (aHR 0.22, 95% CI 0.07–0.71), but no significant differences were seen in noninfectious inflammatory disorders (aHR 0.74, 95% CI 0.48–1.15) or all-cause mortality (aHR 0.55, 95% CI 0.19–1.54). The symptom duration may be used to guide the diagnostic workup among patients with FUO and IUO, in particular those with longstanding symptoms. [ABSTRACT FROM AUTHOR]

We describe a 63-year-old man who presented with an inflammatory aortic aneurysm. The patient had p-ANCA antibodies directed against myeloperoxidase. A diagnosis of idiopathic periaortitis was made. Seven years later, he was rehospitalized because of fever, weight loss, and polyneuropathy. After revision of the aortic biopsy, which showed necrotizing vasculitis with palisading granuloma, a diagnosis of Wegener’s granulomatosis (WG) was made. This case report illustrates an unusual disease course in WG, resembling large vessel vasculitis, and we discuss the possible mechanisms of large vessel involvement in this form of vasculitis. [ABSTRACT FROM AUTHOR]

A revision of the criteria of fever of unknown origin (FUO), established in 1961, is desirable because of important evolutions in medical practice and the emergence of new patient populations. The development of rapid laboratory tests and powerful diagnostic tools, such as ultrasonography, computed tomography and magnetic resonance imaging often makes hospitalization unnecessary and new categories of patients such as those with HIV infection, neutropenia, immunosuppression and nosocomial illness require an approach different from classical FUO. The more then 200 reported causes of FUO can be classified into four diagnostic categories; infections, tumours, noninfectious inflammatory diseases (NIID) and miscellaneous. A uniform classification system is highly wanted to allow comparison between different series. The reports of the 1990s show slight changes in the distribution of causes, namely less infections, less tumours, more NIID and more undiagnosed cases. A uniform diagnostic strategy cannot be determined. The initial investigation should be directed by potentially diagnostic clues revealed by extensive history, meticulous physical examination and a standard set of laboratory tests. 18Fluoro-deoxy-glucose-positron-emitted-tomography is a new valuable total body scintigraphy in the search for the site of origin of the fever. In view of the rather good long-term prognosis, a wait-and-see strategy may be more appropriate than a systematic staged approach. Elderly patients and patients with episodic fever represent two specific groups of classical FUO that require a distinct approach. HIV-associated, nosocomial and neutropenic FUO should be considered as separate clinical entities. [ABSTRACT FROM AUTHOR]

Evaluates the use of positron emission tomography (PET) with 18F-glucose in giant cell arteritis and polymyalgia rheumatica. Polymyalgia rheumatica as a clinical syndrome of proximal muscle pain and stiffness in older patients; 18F-glucose PET scanning as a useful tool for the evaluation of patients with atypical presentations of giant cell arteritis.

(D) Schematic representation of clinical events for each patient We report on three patients who were diagnosed with DADA2 in adulthood. (B) Cellulitis of the hand during a neutropenic phase in patient 1 (left); small bowel perforation on laparoscopy in patient 2 (middle); cicatricial alopecia in patient 3 (right). Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive disease caused by loss-of-function mutations in I ADA2 i that result in a monogenic vasculitis syndrome ([1]). [Extracted from the article]

• Elevated IgG4 levels and IgG4/IgG ratios are not specific for IgG4-RD. • IgG4-RD causes most elevated IgG4 levels high above the upper limit of normal. • Even at very high serum IgG4 levels, 25% of patients did not have IgG4-RD. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus can be complicated by the antiphospholipid syndrome (APS). The clinical manifestations of this syndrome most often documented thus far are recurrent deep venous thrombosis, recurrent spontaneous abortions, and cerebral vascular accidents. Abdominal ischemic events have received relatively little attention in prior reports. We report on a lupus patient with lupus anticoagulant positivity who presented with abdominal pain, anorexia, and weight loss who was subsequently diagnosed with gastric ulcers and pancreatitis. Computerized tomography of the abdomen in addition revealed splenic and kidney infarcts. We conclude that this patient had (ischemic) chronic pancreatitis with pseudocysts and splenic and renal infarcts probably due to secondary APS. [ABSTRACT FROM AUTHOR]

Le syndrome VEXAS (Vacuoles, E1 ubiquitine ligase, liée à l'X, syndrome Auto-inflammatoire, mutation Somatique) est un syndrome auto-inflammatoire lié à des mutations somatiques du gène UBA1. La réalisation d'une tomographie par émission de positrons (TEP) est fréquente au cours du bilan diagnostique de ces patients. Cependant, les anomalies détectées par la TEP ne sont pas bien décrites. Nous avons réalisé une étude multicentrique rétrospective en France et en Belgique, ayant inclus les patients atteints de syndrome VEXAS, défini par l'existence d'un syndrome auto-inflammatoire et d'une mutation somatique du gène UBA1 , chez qui une TEP a été effectuée. Les informations cliniques, biologiques, génétiques et de la TEP ont été recueillies par les médecins en charge des patients. Cent six TEP ont été réalisées chez 57 patients avec syndrome VEXAS. Tous les patients étaient des hommes, avec un âge médian de 71 (écart interquartile : 66–76) ans lors des premiers symptômes et 75 (69–79) au diagnostic de VEXAS. Les manifestations cliniques les plus fréquents étaient des lésions cutanées (86 %), de la fièvre (79 %), des arthralgies/arthrites (68 %), une atteinte pulmonaire (46 %), des chondrites (37 %), et des thromboses veineuses récidivantes (33 %). Sur l'ensemble des TEP, seules 29 % étaient réalisées en l'absence de traitement par corticoïdes et/ou immunosuppresseur, la majorité recevant des corticoïdes dans 66 % et/ou un immunosuppresseur dans 40 %. L'ensemble des TEP montrait une captation anormale du FDG au niveau médullaire chez 82 % des patients, des ganglions chez 54 %, des poumons chez 37 % et de la rate chez 30 % des patients. Plus rarement, il était retrouvé un hypermétabolisme de la plèvre chez 18 %, des cartilages chez 9 %, des articulations chez 5 % et du péricarde chez 2 %. Une vascularite des gros vaisseaux était retrouvée chez 12 % des patients, dont 5 % avec une atteinte de l'aorte et 9 % une atteinte asymétrique des artères (artère brachiale n = 1, artère carotide commune n = 1, artère carotide interne n = 1, artère fémorale profonde n = 1, artère iliaque externe n = 1, vaisseaux de taille moyenne membres supérieurs et inférieurs n = 1). Les TEP réalisées en phase active de la maladie inflammatoire montraient significativement plus d'anomalies que chez les patients en phase de rémission ou de contrôle de la maladie (nombre médian d'anomalies 3 (IQR : 2–4) en phase d'activité versus 1 (IQR : 1–2) en phase d'inactivité ; p < 0,001). Cependant, un hypermétabolisme restait fréquemment détecté en phase d'inactivité au niveau de certains organes, en particulier un hypermétabolisme de la moelle osseuse (70 %), des ganglions (35 %), des poumons (20 %), et des gros vaisseaux (10 %). Parmi les TEP réalisées en phase active de la maladie, il y avait une tendance à avoir plus d'anomalies chez les patients appartenant aux clusters inflammatoire (n = 17 ; médiane 3 [IQR : 2–5]) et hématologique avec syndrome myélodysplasique (n = 24 ; médiane 3 [IQR : 2–4]), comparativement au cluster léger-à-modéré (n = 7 ; médiane 1 [IQR : 1–4]) (p = 0,09). Cette étude décrit les anomalies observées à la TEP au cours du syndrome VEXAS, retrouvant fréquemment des anomalies mais le plus souvent non spécifiques. Les anomalies observées étaient plus fréquentes en phase active de la maladie, mais un hypermétabolisme médullaire persistait chez la plupart des patients suggérant la persistance d'une activité infra-clinique. [ABSTRACT FROM AUTHOR]

Background: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.Methods: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed.Results: Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week.Conclusions: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .). [ABSTRACT FROM AUTHOR]

Polyarteritis nodosa (PAN) is a necrotising vasculitis of medium-sized vessels of unknown origin. This type of vasculitis is usually systemic, but restriction to a single organ, for example the testis, the appendix or the gall bladder, can occur. Testicular pain or tenderness are frequent clinical features. In this report, we present three cases of PAN. In every patient, testicular pain was the main symptom or first sign of systemic disease. We state that a thorough history taking, clinical examination and biochemical analyses are obligatory in patients presenting with acute or chronic scrotal pain. Polyarteritis nodosa should always be taken into account, and a search for systemic spread is mandatory. We emphasize that before initiation of systemic therapy with corticosteroids and/or cyclophosphamide, a Five Factor Score should be obtained, which also gives crucial prognostic information. [ABSTRACT FROM AUTHOR]

Two elderly female patients with fatal calciphylaxis, despite nearly normal renal functions, occurring during treatment for giant cell arteritis, are described. The possible mechanisms for this association are discussed. [ABSTRACT FROM AUTHOR]

A substantial number of cases of polyarteritis nodosa (PAN) are related to hepatitis B virus (HBV) infection. Different treatment strategies are reported in the literature. The aim of this study was to review 15 years of literature (1988–2002) to determine the optimal treatment for HBV-related PAN at present, and to discuss the indications and mechanism of action of corticosteroids in HBV-related PAN, as many physicians are reluctant to use these in the presence of HBV infection. The first patient stopped his initial treatment, relapsed and died of cerebral infarction. The second case illustrates the favorable outcome with the standard treatment: corticosteroids, lamivudine and plasma exchanges. If adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN. Corticosteroids diminish inflammation and corticosteroid withdrawal induces an alanine aminotransferase (ALT) rebound in patients with a low baseline ALT level. Antiviral agents are essential, as they reduce the production of HBV antigens and help to achieve hepatitis B early antigen (HBeAg) seroconversion. Plasma exchanges reduce the level of circulating immune complexes and are included in the treatment protocol of all recent studies. However, their effect has not been evaluated in controlled trials. We concluded that if adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN. [ABSTRACT FROM AUTHOR]

La vascularite urticarienne hypocomplémentémique (VUH) est un syndrome rare associant une urticaire récidivante, une vascularite leucocytoclasique sur la biopsie cutanée et une hypocomplémentémie. L'atteinte d'autres organes est fréquente. Parmi ces manifestations extracutanées, une atteinte pulmonaire spécifique à type de trouble ventilatoire obstructif (TVO) a été décrite mais les données sur cette atteinte sont exceptionnelles. Nous rapportons les caractéristiques de l'atteinte pulmonaire chez les patients atteints de VUH. Cette étude rétrospective multicentrique a inclus des patients ayant un diagnostic de VUH dont le diagnostic a été posé entre 2004 et 2019, et un trouble ventilatoire obstructif défini sur les épreuves fonctionnelles respiratoires par un rapport VEMS/CVF < 70 %. Les données démographiques, cliniques, biologiques, thérapeutiques et évolutives ont été analysées. Nous avons inclus 10 patients (8 femmes et 2 hommes), avec un âge médian de 60,5 (39–77) ans. La VUH était isolée dans 9 cas (90 %) et associée à une thyroïdite d'Hashimoto dans 1 cas (10 %). L'atteinte cutanée consistait en une urticaire associée à des angio-œdèmes dans 80 % et un purpura dans 30 %. Les autres manifestations extracutanées étaient : atteinte ophtalmologique dans 70 %, signes généraux dans 60 %, atteinte rénale dans 20 % et atteinte digestive dans 20 %. Sur le plan pulmonaire, les patients étaient symptomatiques dans tous les cas, avec une dyspnée retrouvée dans 90 %, une toux dans 50 % et une spasticité dans 70 %. Quatre-vingt-dix pour cent des patients étaient fumeurs actifs ou sevrés, avec une consommation médiane estimée à 20 (5–40) paquets-années. Le VEMS/CV médian au diagnostic du TVO était de 60 (27–70) % avec un VEMS médian à 45 (27–81) %. Le TDM thoracique était anormal dans 70 % des cas, retrouvant comme principales anomalies : emphysème dans 57 %, dilatation des bronches dans 57 %, perfusion mosaïque dans 28 %. Le nombre médian de lignes thérapeutiques reçues par ces patients était de 4 (2–6) témoignant du caractère sévère et réfractaire. L'ensemble des patients ont reçu une corticothérapie avec une dose médiane de 45 (20–80) mg/j. Parmi les immunosuppresseurs reçus, on retrouvait : hydroxychloroquine dans 80 %, colchicine ou dapsone dans 40 %, mycophénolate mofétil dans 60 %, cyclophosphamide dans 40 %, rituximab dans 40 %, azathioprine dans 30 % et ciclosporine dans 10 %. Seuls 2 patients n'ont pas reçu de traitement immunosuppresseurs. Après un suivi médian de 111 (33–211) mois, 60 % avait été hospitalisé en urgence pour une exacerbation, dont un tiers en réanimation. La moitié des patients ont présenté une pneumopathie infectieuse, 20 % ont nécessité une oxygénothérapie de longue durée et 30 % la mise en place d'une ventilation non-invasive. Au dernier suivi, le VEMS médian était de 32 (20–81) %, 2 patients étaient inscrits sur liste de transplantation pulmonaire, et une patiente était récusée de l'inscription sur liste du fait de l'état général. Enfin, deux patientes sont décédées, une de l'évolution de son TVO et l'autre d'une cardiopathie ischémique. Le VEMS médian au dernier suivi pour les patients vivants était de 41 (20–81) %. Les troubles ventilatoires obstructifs au cours des VUH sont dans la grande majorité très sévères et surviennent chez des patients fumeurs. Cette atteinte est réfractaire à la plupart des traitements immunosuppresseurs, avec un risque important de décès ou la nécessité de recourir à la transplantation pulmonaire. L'arrêt du tabac au cours du diagnostic de VUH semble ainsi être une priorité absolue vue la sévérité de cette atteinte. [ABSTRACT FROM AUTHOR]

Près de la moitié des patients atteints d'artérites à cellules géantes (ACG) rechutent sous corticothérapie seule. Le taux de rechute semble plus refléter la durée de la corticothérapie que la dose initiale. Cependant, le taux de rechute varie considérablement dans les études observationnelles et les essais contrôlés randomisés. L'objectif était d'identifier les facteurs prédictifs de rechute chez des patients ayant une ACG, inclus dans 3 cohortes internationales distinctes. Cette étude internationale a inclus des patients âgés de plus de 50 ans, remplissant les critères ACR pour le diagnostic d'ACG suivis en France (n = 351), aux États-Unis (n = 285) et en Italie (n = 142). Le critère de jugement principal était le délai entre le diagnostic et la première rechute ou le décès. La survie sans rechute était estimée par la méthode de Kaplan–Meier. Les modèles à risques proportionnels de Cox ont été stratifiés par cohorte. La performance du modèle a été évaluée à la fois par la concordance statistique et par la courbe d'étalonnage. Le modèle final a été présenté avec les hazard ratios (HR) obtenus après ajustement avec leurs intervalles de confiance à 95 % (IC95 %). Nous avons inclus 778 patients (24 % d'homme ; âge médian 71 [EIQ 61–78] ans). Le suivi médian était de 51 [EIQ 24–102] mois. Après 36 mois de suivi, 382 patients ont rechuté, avec une survie sans rechute à 36 mois de 45,3 % (IC95 % : 41,6–49,2), avec des différences marquées entre les cohortes. Les cohortes française et italienne avaient de meilleurs taux de survie sans rechute que la cohorte américaine. Le modèle final corrigé comprenait les céphalées (HR : 1,18, IC95 % : 1,00–1,39 ; p = 0,052), la présence d'une claudication des membres (HR : 1,34, IC95 % : 0,95–1,89 ; p = 0,091), la présence d'une aortite (HR : 1,20, IC95 % : 0,97–1,48 ; p = 0,096) et le taux de CRP (après transformation logarithmique) (HR : 1,11, IC95 % : 1,02–1,22 ; p = 0,014). Le modèle était bien calibré mais avec une capacité de discrimination relativement limitée. Nous avons mis en place un nomogramme permettant d'estimer la survie sans rechute à 3 ans. Des points (allant de 0 à 100) sont attribués à chacune des quatre variables précédentes. Le score total (allant de 0 à 200) est utilisé pour prédire la survie sans rechute à 3 ans dans chaque cohorte. Le risque de rechute de l'ACG est variable selon les centres. Un modèle comprenant les céphalées, la claudication des membres, la présence d'une aortite et l'élévation de la CRP pourrait aider à identifier les patients à haut risque de rechute. Cependant, ce modèle a une faible capacité de discrimination, possiblement due à l'hétérogénéité observées entre les cohortes. [ABSTRACT FROM AUTHOR]

Abstract: Exceptionally, gastrointestinal involvement of Churg-Strauss syndrome (CSS) may require extensive bowel resection resulting in a short bowel syndrome. Living related intestinal transplantation (IT) has emerged as an alternative to deceased-donor IT in the management of patients with irreversible short bowel syndrome. Herein, we have presented a 35-year-old patient with isolated intestinal involvement of CSS lesions refractory to steroids and azathioprine requiring multiple abdominal resections resulting in an ultrashort bowel syndrome. A living related IT (from the mother) was performed. She underwent several acute rejection episodes treated with additional immunosuppressive therapy. Despite higher doses of immunosuppression, these repeated acute rejection episodes eventually evolved into a syndrome of chronic allograft rejection. Eventually, owing to her poor general condition and to avoid life-threatening infections, transplantectomy was inevitable. Recent immunologic studies indicate that peripheral mononuclear cells from patients with CSS secrete large amounts of T-helper type 1 and 2 cytokines. It is likely that patients with CSS are at higher risk for acute and chronic rejection after transplantation. [Copyright &y& Elsevier]

Presents a letter to the editor in response to comments on doppler ultrasonography of the temporal arteries.

Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR)., Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated., Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care., Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR., Competing Interests: Competing interests: KKK: Research grants from Independent Research Fund Denmark, Danish Rheumatic Association and Central Denmark Region unrelated to this project. SES: Research grants from Rheumatology Research Foundation, Bristol Myers Squibb Foundation. Clinical trial support from AstraZeneca, GlaxoSmithKline; Consulting fees from Sanofi (funds toward research support); Data Safety Monitoring Board on MINT trial, Advisory Board for Sanofi (funds toward research support). E-MH: Has received grants unrelated to this manuscript from Novo Nordic Foundation, Roche, Novartis; Personal fees from AbbVie, Sanofi, SOBI, Merck Sharp & Dohme and Union Chimique Belge. AD: Consulting fees from Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi; Board member Vasculitis Foundation. LN: Has received Honorarium from Abbvie; Trustee of the charity PMR-GCA Scotland. SM: Consulting fees from Astrazeneca; Honoraria from Vifor. KJW: Grants from Eli Lilly, Kiniksa, BMS; Consulting fees from Amgen, Sanofi. Honoraria from Amgen. CP: Consulting fee from Pfizer. MP: Consulting fee from Novartis; Clinical trial participant for Abbvie, Amgen, AstraZeneca. HIK: Honoraria from Roche, eTherapeutic Guidelines Australia; Board member Australian Rheumatology Association; Clinical trials for Roche, Abbvie, Sun, Emerald, Novartis, Biogen, Sanofi, Syneos. CEO: Consultancy for Abbvie; Speaking honoraria from Abbvie, Janssen, Novartis and Roche; Advisory board for Abbvie. WAS: Has received honoraria from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi ; Support for attending meetings/travel from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi; Participated in advisory board from Abbvie, GlaxoSmithKline, Novartis, Sanofi; Principle investigator of phases 2 and 3 studies sponsored by Abbvie, GlaxoSmithKlinie, Novartis and Sanofi. EBrouwer: As an employee of the UMCG received a speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands in 2023 which was paid to the UMCG; As an employee of the UMCG received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514 which were paid to the UMCG. SM: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SM is supported in part by the NIHR Leeds Biomedical Research Centre. VD-P has received honorarium from Abbvie, Chugai, Novartis, BMS, Support for attending meetings/travel from Novartis; Participated in advisory borad from Abbvie, Novartis. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms., Methods: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively., Results: We included 398 GCA patients, of which 181 (45%) with PMR symptoms. Patients with PMR symptoms had a longer symptom duration (11 vs 6 weeks, p < 0.001). They less frequently reported fever (19% vs 28%, p = 0.030) and fatigue (52% vs 64%, p = 0.015) and tended to have less permanent vision loss (12% vs 19%, p = 0.052). There was no difference in the cumulative oral GC dose at 2 years (4.4 vs 4.3 g methylprednisolone, p = 0.571). However, those with PMR symptoms were treated with higher GC doses during subsequent follow-up (p < 0.05 from 38 months after diagnosis) and had a lower probability of stopping GC (62% vs 71%, HR 0.74 [95%CI 0.58-0.94], p = 0.018) with a longer median duration of GC treatment (29 vs 23 months, p = 0.021). In addition, presence of PMR symptoms was associated with an increased risk of relapse (64% vs 51%, HR 1.38 [95%CI 1.06-1.79], p = 0.017) with a higher number of relapses (1.47 [95%CI 1.30-1.65] vs 1.16 relapses [95%CI 1.02-1.31], p = 0.007). Patients with PMR symptoms less frequently developed thoracic aortic aneurysms during follow-up (3% vs 11%, p = 0.005)., Conclusion: GCA patients with PMR symptoms had more recalcitrant disease with a higher risk of relapse and longer duration of GC treatment with need for higher GC doses., Competing Interests: Declaration of competing interest LM: Abbvie, Roche; AB: None; LB: None; GM: None; KVL: None; EDL: AC Immune, Actelion, Astra Zeneca, Boehringer Ingelheim, GSK, Novartis, Otsuka; SV: None; DB: Eli Lily, GSK, Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without large vessel vasculitis (LVV) and according to the extent and severity of LVV., Methods: Consecutive patients diagnosed with GCA between 2003 and 2020 who have had FDG PET imaging at diagnosis ≤3 days after initiation of glucocorticoids and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively. PET scans were visually scored (0-3) in 7 vascular areas and a total vascular score (TVS) was calculated. LVV was defined as FDG uptake ≥2 in any large vessel., Results: We included 238 GCA patients, of which 169 (71%) had LVV. LVV patients were younger (69 vs 74 years, p< 0.001) and more frequently female (72% vs 49%, p= 0.001). In patients without PMR symptoms, the presence of LVV was associated with relapse (aOR 3.05 [95%CI 1.32-7.43], p= 0.011) and with a lower probability of stopping glucocorticoids (aHR 0.59 [95%CI 0.37-0.94], p= 0.025). However, in those with PMR symptoms, there was no difference in relapse risk (aOR 1.20 [95%CI 0.53-2.66], p= 0.657) and in the probability of stopping glucocorticoids (aHR 1.25 [95%CI 0.75-2.09], p= 0.394) between patients with and without LVV. A higher TVS was associated with an increased risk of relapse (aOR 1.09 [95%CI 1.04-1.15], p= 0.001] in patients without PMR symptoms, but not in those with PMR symptoms (aOR 1.01 [95%CI 0.96-1.07], p= 0.693)., Conclusion: LVV is a risk factor for relapse in GCA patients without PMR symptoms with a higher relapse risk in those with higher TVS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci., Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings., Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10 -8 ; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10 -9 ; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10 -8 ; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10 -13 )., Interpretation: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis., Funding: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research., Competing Interests: Declaration of interests MCC reports support from the Spanish Ministry of Science and Innovation (PID2020-114909RB-I00), Vasculitis Foundation, Agency for the Management of University and Research Grants (2021 SGR 01561), and Kiniksa Pharmaceuticals; consulting fees or honoraria from GSK, CSL Vifor, AbbVie, and AstraZeneca; support for attending meetings from Kiniksa Pharmaceuticals; and participation on a data safety monitoring board or advisory board for GSK, CSL Vifor, and AstraZeneca. GE has acted as a consultant for GSK, AstraZeneca, Sobi, Novartis, Boehringer, and CSL Vifor. AWM reports support from the UK Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), Leeds Care, and Roche Products; and consulting fees or honoraria from CSL Vifor and AstraZeneca. PL reports grants or contracts from the Federal Ministry of Education and Research, German Research Society, German Society for Rheumatology, John Grube Foundation, and CSL Vifor; consulting fees or honoraria from GSK, CSL Vifor, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Forum für medizinische Fortbildung, Janssen, Rheumaakademie, and UCB; support for attending meetings from CSL Vifor; and participation on a data safety monitoring board or advisory board for GSK, CSL Vifor, AbbVie, and Novartis. TW reports consulting fees or honoraria from AbbVie, AstraZeneca, Lilly, UCB, and Novartis; and participation on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Lilly, UCB, Novartis, and Fresenius. MAG-G reports honoraria from GSK. NK reports grants or contracts from Bristol Myers Squibb, AbbVie, and Sanofi; and consulting fees or honoraria from Roche, Otsuka, GSK, and Mallinckrodt. CAL reports grants or contracts from Bristol Myers Squibb and support from the National Institutes of Health. PAM reports grants, contracts, or consulting fees from AbbVie, Amgen, AstraZeneca, ArGenx, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, CSL Behring, Eicos, Electra, Forbius, Genentech–Roche, GSK, HiBio, InflaRx, Janssen, Jubilant, Kyverna, MiroBio, Neutrolis, Novartis, NS Pharma, Q32, Regeneron, Sanofi, Sparrow, Takeda, and Vistera; royalties or licenses from UpToDate; and stock or stock options from Kyverna, Q32, and Sparrow. SLM reports grants or contracts from MRC, NIHR, and CSL Vifor; consulting fees from Roche, Sanofi, AbbVie, AstraZeneca, and Pfizer; payment or honoraria for lectures or educational events from Roche, Pfizer, UCB, CSL Vifor, Fresenius Kabi, and Novartis; support for attending meetings from Pfizer; participation on a data safety monitoring board or advisory board for Collaboration for Leadership in Applied Health Research and Care, Haywood Foundation, and GC-SheaLD; a leadership or fiduciary role in the British Society for Rheumatology Clinical Affairs Committee; participation as an investigator on industry-sponsored clinical trials for Sanofi; and infrastructure support from MRC. LB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Instrumentation Laboratory SPA and AbbVie; and support for attending meetings from AbbVie and Novartis. EB reports payments or honoraria from EULAR and received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514. EB is member of the board of the non-profit organisation, Auto-immune Research Hub, in the Netherlands. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up., Methods: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models., Results: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I 2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I 2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I 2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I 2 0 %)., Conclusion: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024. Published by Elsevier B.V.)