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Episodic angioedema with eosinophilia (EAE) (Gleich syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia, and frequent elevated serum IgM level. We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. A total of 30 patients with a median age at diagnosis of 41 years (range, 5-84) were included. The median duration of each crisis was 5.5 days (range, 1-90), with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%), of whom 5 (17%) showed evidence of clonal T-cell receptor gamma locus gene (TRG) rearrangement. The median duration of follow-up was 53 months (range, 31-99). The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio, 4.15; 95% confidence interval, 1.18-14.66; P =.02). At last follow-up, 3 patients (10%) were able to have all treatments withdrawn and 11 (37%) were in clinical and biologic remission with less than 10 mg of prednisone daily. EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is a large-vessel vasculitis that mainly affects women over fifty. GCA usually involves branches from the external carotid arteries, causing symptoms such as headaches, scalp tenderness, and jaw claudication. The most severe complication is ophthalmologic involvement, including acute anterior ischemic optic neuropathy and, less frequently, central retinal artery occlusion with a risk of permanent blindness. Approximately 40% of patients may have involvement of the aorta or its branches, which has a poor prognosis, although this is often asymptomatic at diagnosis. Diagnosis is largely based on imaging techniques such as FDG-PET combined with CT, CT angiography, or MRI angiography of the aorta and its branches. Polymyalgia rheumatica is associated with GCA in 30–50% of cases but may also occur independently. Treatment must be initiated urgently in the presence of ophthalmologic signs or when GCA is strongly suspected to prevent vision loss. The gold standard to confirm the diagnosis is temporal artery biopsy. However, Doppler ultrasound and vascular imaging are also reliable diagnostic techniques. Initially, high doses of corticosteroids like prednisone (40–80 mg per day) are the mainstay of treatment. Tocilizumab can be discussed in combination with prednisone for corticosteroid sparing. Long-term management is essential, including monitoring for disease recurrence and corticosteroid-related side effects. General practitioners play a crucial role in early diagnosis, directing patients to specialized centres, and in managing ongoing treatment in collaboration with specialists. This collaboration is essential to address potential long-term complications such as cardiovascular events. They can occur five to ten years after the diagnosis of GCA even when the disease is no longer active, meaning that vigilant follow-up is required due to the patients' age and status. [ABSTRACT FROM AUTHOR]

An updated revision of the 2016 recommendations from the French Study Group for Large Vessel Vasculitis (GEFA) was needed to better delineate the place and management of immunosuppressants or biologics in giant cell arteritis (GCA). A panel of 18 physicians, including internists and rheumatologists, constituted the task force of this project and drafted the recommendations. Twelve additional readers were asked to analyse and comment on the recommendations. Two face-to-face virtual meetings were held to discuss and validate the recommendations. Each member voted individually, and a > 85% consensus was required to validate each recommendation. From the initial 6 questions, 26 recommendations were validated. The following main recommendations were validated. (1) Subcutaneous 162 mg tocilizumab (TCZ) for at least 12 months should be used first when glucocorticoid (GC)-sparing treatment is needed with the objective of discontinuing GCs within the subsequent 6 months. (2) GCA patients who have experienced any of the following conditions must receive TCZ at GCA diagnosis with 6 months of GC therapy: major cardiovascular event, osteoporosis with fracture, psychiatric event with GC use, complicated diabetes mellitus, or any previous > 6 months of GC treatment. (3) In patients in whom GC discontinuation is not possible after 12 months of treatment because of persistent disease activity or in patients in whom GC-related adverse events are unacceptable, TCZ (or alternatively methotrexate) may be proposed. These recommendations were constructed based on the results of the published literature and the experts' experiences to standardise therapeutic practices in France. Further updates will likely be necessary following new publications. [ABSTRACT FROM AUTHOR]

• Giant-cell arteritis-related aortic dissection occurs earlier in patients with aortitis than in those without. • 70% of patients presented Stanford type A aortic dissection. • Half of patients with type a dissection had a previous thoracic aorta dilation. • Aortic surgery is the single predictive factor for survival in patients with GCA-related aortic dissection. To describe characteristics and outcomes of patients with giant cell arteritis (GCA)-related aortic dissection. We retrospectively included, through a nationwide GCA network, all patients who had an aortic dissection either revealing GCA or occurring during follow-up. A total of 46 patients were included in this study. Aortic dissection was inaugural and led to GCA diagnosis in 21 patients, whereas it occurred during follow-up in the 25 others, at a median of 53 [1–265] months after GCA diagnosis. Large-vessel vasculitis (LVV) was diagnosed through imaging before or at the time of aortic dissection in 31 (67%) patients. In patients who developed an aortic dissection during follow-up, the aortic event occurred 22 [1–143] months post GCA diagnosis in the patients with previous aortitis, whereas it occurred after 72 [19–265] months in patients without previously diagnosed aortitis (p = 0.005). Aortic surgery was performed in 27 (59%) patients and 23 of them survived. A total of 15 (32%) patients died following the aortic dissection, including 11 who were not operated on. In a multivariate analysis, aortic surgery was the single predictor of survival (HR: 4.3; 95% CI: 1.47— 15.7; p = 0.007). Patients with prior LVV are more prone to develop early aortic dissection and require close monitoring of aortic morphology. One third of patients died from the aortic dissection. Surgery remains the best predictive factor for survival. [ABSTRACT FROM AUTHOR]

• GCA patients with scalp, tongue and/or lip necrosis have more cephalic symptoms but not more ocular involvement after matching for sex, age at diagnosis and diagnosis period. • GCA patients with scalp, tongue and/or lip necrosis display shorter overall survival. • Scalp tenderness and cognitive disorder at diagnosis seem to be factors significantly associated to this very rare complication of GCA. Scalp, tongue and/or lip necrosis are rare complications of GCA. To describe characteristics and outcome of patients with giant cell arteritis (GCA) -related scalp, tongue and/or lip necrosis. A retrospective nationwide multicenter study included 20 GCA patients with scalp, tongue, and/or lip necrosis diagnosed between 1998 and 2021 and 80 GCA control patients matched for age, sex and management period. Logistic regression analyses were conducted to identify baseline characteristics associated with scalp, tongue and/or lip necrosis. Compared to controls, patients with scalp, tongue and/or lip necrosis showed significantly more cranial manifestations (headache, p=0.045; scalp tenderness, p=0.006; jaw claudication, p=0.02). No differences were observed between both groups regarding the occurrence of visual symptoms or large vessel involvement. At diagnosis, GCA patients with necrosis more likely received IV methylprednisolone infusions and higher doses of oral prednisone. There were no differences regarding vascular complications during follow up. Compared to controls, survival was decreased in GCA patients with necrosis (p=0.003). In a multivariable logistic regression model, scalp tenderness [odds ratio (OR) 4.81(95 % CI: 1.57, 14.79), p = 0.006] and cognitive disorder [OR 6.42 (95 % CI: 1.01, 40.60), p=0.048] were identified as factors associated to scalp, tongue, and/or lip necrosis. Our results suggest that scalp, tongue, and/or lip necrosis is associated to higher mortality in GCA patients. Scalp tenderness and cognitive disorder were significant factors associated to this very rare complication of GCA. [ABSTRACT FROM AUTHOR]

Objectives To assess the prevalence of bronchiectasis in a Western cohort with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) and its correlations with disease presentation and outcome. Methods Retrospective study of ANCA-associated vasculitis (AAV) patients followed at Nantes University Hospital (2005–2015). Clinical, biological, and follow-up data were collected through chart review. Two experienced radiologists blinded to the clinical data interpreted chest high-resolution CTs according to the Feischner Society criteria. Results Fifty-eight patients were included: 30 had MPA (51.7%) and 28 had GPA (48.3%). The median age at AAV diagnosis was 65.5 years. Anti-MPO-ANCA and anti-PR3-ANCA were present in 39 (67.2%) and 19 (32.8%) patients, respectively. Overall, bronchiectasis was found in 22 patients (37.9%), all of whom had anti-MPO ANCA. In multivariate analysis, bronchiectasis was independently associated with anti-MPO-ANCA, female gender and age at AAV diagnosis. Furthermore, anti-MPO ANCA patients with bronchiectasis had more frequent peripheral nerve involvement (54.5 vs. 17.6%, p = 0.019) and less frequent renal involvement than those without bronchiectasis (40.9% vs. 82.3%, p = 0.009). Disease course, survival and risk of severe pulmonary infection were similar in patients with and without bronchiectasis on chest CT. Conclusions This study shows that bronchiectasis is a highly prevalent pre-existing respiratory condition in Caucasian patients with anti-MPO AAV. This subset of patients exhibits a distinct presentation. Further studies are needed to confirm these findings and clarify the clinical implications of this association. Whether the respiratory tract could be the site of initiation of anti-MPO auto-immunity remains to be investigated. [ABSTRACT FROM AUTHOR]

Résumé La consommation de cocaïne est un piège étiologique récurrent dans le champ des vascularites systémiques. Dès les années 1990 a été soulevée la possibilité de survenue de lésions ORL mimant une granulomatose avec polyangéite localisée accompagnées d’anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA), dirigés contre la protéinase 3 (PR3) et la human neutrophil elastase (HNE). Plus récemment, la cocaïne coupée au lévamisole a été responsable, en Amérique du Nord puis dans le reste du monde, de multiples cas de vasculopathie cutanées voire systémiques associées à des ANCA, avec fréquemment une double positivité, anti-myéloperoxydase et anti-PR3, et d’autres auto-anticorps. Les particularités cliniques et immunologiques de ces tableaux toxiques doivent être connues. La physiopathologie de ces affections reste imparfaitement élucidée mais pourrait nous permettre de mieux comprendre les mécanismes de la rupture de tolérance à l’œuvre dans les vascularites à ANCA classiques. Cocaine use is a multifaceted diagnostic pitfall in the field of systemic vasculitides. The fact that Cocaine-Induced Midline Destructive Lesions (CIMDL) can be associated with Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and mimic localized granulomatosis with polyangitis is known for decades. In these cases ANCA target Proteinase 3 (PR3) and Human Neutrophil Elastase. More recently, levamisole adulterated cocaine has been implicated in a peculiar clinico-biological syndrome combining cutaneous vasculopathy and sometimes glomerulonephritis, and ANCA positivity with frequent double positivity (PR3 and myeloperoxydase). Clinician should be aware of the clinical and immunological hints to these diagnoses. The pathogenesis of such drug-induced auto-immune syndromes is poorly understood. Its studying may shed new light on the potential mechanism involved in tolerance breakdown in conventional ANCA-associated vasculitides. [ABSTRACT FROM AUTHOR]

Objectives Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan. Methods ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. Results Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 ( p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 ( p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 ( p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 ( p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI ( p = 0.04), CHFS ( p = 0.04), and pain score ( p = 0.046). Conclusions In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability. [ABSTRACT FROM AUTHOR]

• Aortitis with an aortic wall thickening on CTA at GCA diagnosis was associated with an increased risk of relapse. • In GCA, relapse rates are high when patients have large vessel vasculitis, in this study the relapse rate of patients with aortitis at diagnosis was 62%. • A good agreement between PET/CT and CTA for the diagnosis of aortitis was observed, with 78% diagnosed by both CTA and PET/CT and 22% only by PET/CT. Prognosis data on giant-cell arteritis (GCA)-associated aortitis are scarce and heterogeneous. The aim of this study was to compare the relapses of patients with GCA-associated aortitis according to the presence of aortitis on CT-angiography (CTA) and/or on FDG-PET/CT. This multicenter study included GCA patients with aortitis at diagnosis; each case underwent both CTA and FDG-PET/CT at diagnosis. A centralized review of image was performed and identified patients with both CTA and FDG-PET/CT positive for aortitis (Ao-CTA+/PET+); patients with positive FDG-PET/CT but negative CTA for aortitis (Ao-CTA-/PET+), and patients solely positive on CTA. Eighty-two patients were included with 62 (77%) of female sex. Mean age was 67±8 years; 64 patients (78%) were in the Ao-CTA+/PET+ group; 17 (22%) in the Ao-CTA-/PET+ group and 1 had aortitis only on CTA. Overall, 51 (62%) patients had at least one relapse during follow-up: 45/64 (70%) in the Ao-CTA+/PET+ group and 5/17 (29%) in the Ao-CTA-/PET+ group (log rank, p = 0.019). In multivariate analysis, aortitis on CTA (Hazard Ratio 2.90, p = 0.03) was associated with an increased risk of relapse. Positivity of both CTA and FDG-PET/CT for GCA-related aortitis was associated with an increased risk of relapse. Aortic wall thickening on CTA was a risk factor of relapse compared with isolated aortic wall FDG uptake. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: Q fever is a worldwide zoonosis caused by Coxiella burnetii. Its presentation can be atypical, delaying and complicating the diagnosis. We report 7 cases of Q fever mimicking vasculitis, systemic inflammatory disease, or auto-immune disorder. Methods: Seven cases of Q fever diagnosed between 1995 and 2007 in Nantes University Hospital (France) are described. They occurred in a nonendemic region and were selected on the basis of initial clinical presentation suggesting systemic immune disease. C. burnetii was detected using indirect immunofluorescence serology. Results: Q fever was acute in 4 of the 7 patients and chronic in 3. None had endocarditis. The initial presentations suggested Crohn''s disease, Goodpasture''s syndrome, polymyalgia rheumatica, adult-onset Still''s disease, polyarteritis nodosa, giant-cell arteritis, and essential type II cryoglobulinemia. Two patients had antiphospholipid antibodies, 1 had transient IgG kappa monoclonal gammopathy, and 1 had polyclonal T CD8+ large granular lymphocyte expansion. Conclusion: Clinicians must be aware of the potential diagnosis of Q fever, and C. burnetii serology is a helpful diagnostic tool in the investigation of fever of unknown origin with atypical systemic symptoms suggesting vasculitis or inflammatory disease. [Copyright &y& Elsevier]

Giant cell arteritis is a diffuse inflammatory disease that affects predominantly superficial temporal arteries but may also concern larger arterial vessels. Vascular explorations may be helpful to the diagnostic strategy and to characterize extension of the disease. The Doppler ultrasonography of the temporal vessels is in most cases less efficient than the useful and well-tolerated temporal artery biopsy for the diagnosis of giant cell arteritis. Vascular explorations of larger arteries lead to detect arterial stenosis affecting predominantly axillar and sub-clavian arteries. Aortitis represents the most serious complication of the disease, because of the risk of aortic dissection or rupture. Aortic complications may be detected with ultrasonography, computed tomography, magnetic resonance imaging or aortography. Screening aortic lesions is not codified, but helical computed tomography could be of interest in this indication. [ABSTRACT FROM AUTHOR]

Giant cell arteritis is characterized by diffuse arterial inflammation that selectively involves the superficial temporal arteries but can occur in larger arteries. Various vascular investigations can assist in diagnosing and evaluating the extent of giant cell arteritis. Imaging techniques, mainly Doppler ultrasonography of the superficial temporal arteries, seem less reliable for the diagnosis than temporal artery biopsy, which is safe and remains indispensable. Investigations of larger arteries can detect asymptomatic stenotic lesions, which are common, particularly in the axillary and subclavian arteries. Involvement of the aorta can cause life-threatening dissection or aneurysmal rupture. Imaging techniques useful for diagnosing aortic involvement include ultrasonography, computed tomography, magnetic resonance imaging, and aortography. Although there is no standardized strategy for aortic lesion detection, helical computed tomography may be valuable. [Copyright &y& Elsevier]

L'aortite est une entité pathologique rare dont la prévalence est inconnue. Les aortites primitives touchent principalement l'aorte thoracique. Elles sont le plus souvent diagnostiquées en imagerie sur une fixation du 18-FDG de grade III de la paroi de l'aorte à la TEP, ou par un épaississement circonférentiel > 2,2 mm à la TDM ou en IRM avec une prise de contraste au temps tardif. Plus rarement, l'aortite est prouvée histologiquement comme dans certains cas d'aortites cliniquement isolées où l'aortite est découverte après une chirurgie programmée d'anévrisme aortique ou lors d'une chirurgie de dissection aortique. Les types histologiques les plus fréquents sont : granulomateux/à cellules géantes ou lymphoplasmocytaires. Les signes cliniques associés aux aortites sont souvent non spécifiques, asthénie, fièvre, toux sèche, douleurs thoraciques, dorsales, lombaires ou abdominales. Les aortites peuvent être réparties dans différents cadres étiologiques : les aortites primitives qui regroupent les vascularites avec un tropisme préférentiel ou exclusif pour la paroi de l'aorte, les aortites secondaires aux maladies de systèmes ou iatrogènes, et les aortites infectieuses. Les principales étiologies des aortites primitives sont l'artérite à cellules géantes (ACG), l'artérite de Takayasu (AT) ou les aortites cliniquement isolées. Les aortites secondaires aux maladies de systèmes sont observées au cours de la polychondrite atrophiante, du lupus systémique ou des rhumatismes inflammatoires comme la spondylarthropathie ou la polyarthrite rhumatoïde. Au cours de l'ACG comme de l'AT, l'aortite est un facteur péjoratif, caractérisée par des risques plus élevés de rechute, de complications cardiovasculaires et une mortalité augmentée. La prise en charge des aortites est insuffisamment codifiée, elle repose sur le contrôle des facteurs de risques cardiovasculaires avec une surveillance particulière de la pression artérielle et du LDL cholestérol, et d'autre part, sur la corticothérapie et les immunosuppresseurs dont l'usage dépendra de la maladie associée à l'aortite, de la gravité initiale et des comorbidités. Aortitis is a rare disease entity of unknown prevalence. Primary aortitis mainly affects the thoracic aorta. They are most often diagnosed on imaging by grade III 18-FDG uptake of the aortic wall on PET, or by circumferential thickening > 2.2 mm on CT or MRI with late-stage contrast. More rarely, aortitis is histologically proven, as in some cases of clinically isolated aortitis discovered after planned aortic aneurysm surgery or during aortic dissection surgery. The most common histological types are granulomatous/giant cell or lymphoplasmacytic. Clinical signs associated with aortitis are often non-specific: asthenia, fever, dry cough, chest, back, lumbar or abdominal pain. Aortitis can be divided into different etiological categories: primary aortitis, which includes vasculitis with a preferential or exclusive tropism for the aortic wall, aortitis secondary to systemic or iatrogenic diseases, and infectious aortitis. The main etiologies of primary aortitis are giant cell arteritis (GCA), Takayasu arteritis (TA) or clinically isolated aortitis. Aortitis secondary to systemic diseases is seen in atrophying polychondritis, systemic lupus and inflammatory rheumatic diseases such as spondyloarthropathy and rheumatoid arthritis. In both ACG and AT, aortitis is a negative factor, characterized by a higher risk of relapse, cardiovascular complications and increased mortality. The management of aortitis is insufficiently codified, and relies on the control of cardiovascular risk factors, with particular monitoring of blood pressure and LDL cholesterol, and on corticosteroid therapy and immunosuppressive drugs, the use of which will depend on the disease associated with the aortitis, the initial severity and comorbidities. [ABSTRACT FROM AUTHOR]

Seven autoantibodies directed against synthetases have been identified to date, the best known being anti-Jo1. Synthetases play a vital role in protein synthesis by catalyzing the acetylation of transfer RNAs (tRNAs). The most common form of antisynthetase syndrome is characterized by anti-Jo1 production, interstitial lung disease (ILD), inflammatory muscle disease, and, in many cases, fever, polyarthritis, Raynaud’s phenomenon, and thick cracked skin on the fingers (mechanic’s hands). The interstitial lung disease is generally of the “usual interstitial pneumopathy” type and shares similarities with idiopathic pulmonary fibrosis or scleroderma-related pulmonary disease. It governs the prognosis of the disease, being associated with an excess mortality rate of about 40%. The pathogenic mechanisms underlying antisynthetase syndrome remain unknown but may involve cell-mediated immunity. The treatment is not standardized. The ILD responds to glucocorticoids in some patients but requires other immunosuppressant drugs in others. [Copyright &y& Elsevier]

The antisynthetase syndrome is caracterized by the severity of the interstitial lung disease. Actually, 7 antibodies from the antisynthetase’s family have been identified. The anti-Jo1 antibody(histidyl tRNA synthetase) is the most usual and associate interstitial lung disease with idiopathic inflammatory myopathy and generally fever, arthritis, Raynaud’s phenomenon and “mechanic’s hand”. The interstitial lung disease of Sas has the same features than idiopathic pulmonary fibrosis and systemic sclerosis, usually of “usual interstitial pneumonia” type. Corticosteroid treatement has usually no efficacy on pulmonary disease and other immunosuppressive drugs are often necessary. [Copyright &y& Elsevier]

Granulomatosis with polyangiitis (GPA) (Wegener’s) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2 years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents. [ABSTRACT FROM AUTHOR]