Search

Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution.To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol.We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG 7 pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM.A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004).Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.

Objectives To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short pulses glucocorticoid (GC) on clinical manifestations and vessel inflammation and damage in large vessel-giant cell arteritis (LV-GCA). Methods In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day methylprednisolone intravenously for three consecutive days and weekly subcutaneous TCZ injections from day 4 until week 52. PET/CT was performed in all patients at baseline and at weeks 24 and 52. The primary endpoints were the reduction of PETVAS at weeks 24 and 52 compared with baseline and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. Results 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction of PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions -8.6 (-11.5 to -5.7) and -10.4 (-13.6 to -7.2), p= 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31–78) and 8/17 (47%, 95% CI 23–72), respectively. At weeks 24 and 52 no patient showed new aortic dilation. However, 4 dilated patients at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. Conclusions TCZ monotherapy after ultra-short GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909.

ObjectiveThe aim was to identify any association between imaging signs of vessel wall inflammation (positron emission tomography–CT (PET-CT) score and CT/MR wall thickening) and synchronous and subsequent vascular damage (stenoses/dilations) in patients with large vessel vasculitis (LVV).MethodsConsecutive patients with LVV referred to a tertiary centre in 2007–2020 with baseline PET-CT and morphological imaging (CT/MR angiography) performed within 3 months were included. All available PET-CT and CT/MR scans were reviewed to assess PET-CT uptake (4-point semi-quantitative score), wall thickening, stenoses and dilations for 15 vascular segments. The associations of baseline PET score and CT/MR wall thickening with synchronous and incident stenoses/dilations at CT/MR performed 6–30 months from baseline were evaluated in per-segment and per-patient analyses. Respective areas under the receiver operating characteristic curve (AUC) were calculated.ResultsWe included 100 patients with LVV (median age: 48 years, 22% males). Baseline PET score and wall thickening were strongly associated (Cuzick non-parametric test for trend across order groups (NPtrend) ConclusionPET score and wall thickening are strongly associated, but only baseline PET score is a good predictor of incident vessel wall damage in LVV.

Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome.

Objectives To evaluate the accuracy of PET/CT and of PET vascular activity score (PETVAS) in assessing disease activity and the ability of PETVAS in predicting relapses in a large single-centre cohort of patients with large vessel vasculitis (LVV). Methods We conducted a retrospective cohort study of prospectively collected data of consecutive patients diagnosed with LVV who underwent at least one PET/CT scan between 2007 and 2020. The nuclear medicine physician’s interpretation of each PET/CT scan (active/inactive vasculitis) was compared with disease activity clinical judgement (active disease/remission). For each PET/CT scan, the PETVAS score was calculated and its accuracy in assessing disease activity was evaluated. The ability of PETVAS in predicting subsequent relapses was evaluated. Results A total of 100 consecutive LVV patients (51 large vessel GCA, 49 Takayasu arteritis) underwent a total of 476 PET/CT scans over a mean follow-up period of 97.5 months. Physician-determined PET/CT grading was able to distinguish between clinically active and inactive LVV with a sensitivity of 60% (95% CI 50.9, 68.7) and specificity of 80.1% (95% CI 75.5, 84.1); the area under the curve (AUC )was 0.70 (95% CI 0.65, 0.75). PETVAS was associated with disease activity, with an age and sex–adjusted odds ratio for active disease of 1.15 (95% CI 1.11, 1.19). A PETVAS ≥10 provided 60.8% sensitivity and 80.6% specificity in differentiating between clinically active and inactive LVV; the AUC was 0.73 (95% CI 0.68, 0.79). PETVAS was not associated with subsequent relapses, with an age and sex–adjusted hazard ratio of 1.04 (95% CI 0.97, 1.11). Conclusions The visual PET/CT grading scale and PETVAS had moderate accuracy to distinguish active LVV from remission. PETVAS did not predict disease relapses.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase=1.79; 95% confidence interval [CI]=1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase=2.24; 95%CI=1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (P Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.

Purpose To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). Methods Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. Results A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. Conclusions The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.

Objective: To assess sensitivity and specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak.Methods: In this cross-sectional study we included all consecutive patients who presented to the ER between March 13th and 23rd for suspected COVID-19 and underwent both CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes.Results: The study included 696 patients (41.4% women; age 59±15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73% to 77% and from 90% to 94% for high and low positivity threshold, respectively. Specificity ranged from 79% to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes.Conclusions: During the outbreak peak, CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation.

To evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB).We studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed.A final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61-1.27) and 1.15 (CI, 0.67-1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59-3.19) and 3.77 (CI, 0.53-26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68-1.25).A large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.

To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA).We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison.37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p0.0001) and the total duration of PDN treatment longer (p0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.002). In the multivariate model fever ≥ 38°C (HR 2.30, 95%CI:1.11-4.78) and total cumulative PDN dose (HR 1.18, 95%CI: 1.08-1.30) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.26, 95%CI: 0.11-0.59) and long-term remission (HR 0.27, 95%CI: 0.11-0.65) with a reduced risk. 35/84 patients (41.6%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.04 and p = 0.002, respectively), and the total cumulative prednisone dose was lower (p0.001) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.21, 95%CI: 0.07-0.62) and the total cumulative PDN dose (HR 0.85, 95%CI: 0.77-0.95) were significantly negatively associated with long-term remission.In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.

Background:Previous studies evaluated clinical relapses and long-term remission mainly in patients with biopsy-proven GCA and/or patients satisfying the ACR 1990 criteria for GCA classification. Also, radiological involvement was unfrequently used to define relapses and monitor disease activity in patients with LV-GCAObjectives:To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA).Methods:We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A comparison group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison.Results:37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p = 0.0001) and the total duration of PDN treatment longer (p = 0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.003). In the multivariate model fever ≥ 38 °C (HR 3.22, 95%CI:1.43-7.27),duration of PDN treatment (HR 1.01, 95%CI: 1.00-1.02) and total cumulative PDN dose (HR 1.20, 95%CI: 1.09-1.33) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.22, 95%CI: 0.09-0.55) and long-term remission (HR 0.30, 95%CI: 0.12-0.75) with a reduced risk. 37 patients (42.5%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.003 for both), and the total cumulative prednisone dose was lower (p = 0.005) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.33, 95%CI: 0.14-0.78) and the total cumulative PDN dose (HR 0.89, 95%CI: 0.83-0.96) were significantly negatively associated with long-term remission.Conclusion:In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.Disclosure of Interests:luigi boiardi: None declared, Francesco Muratore: None declared, Giovanna Restuccia: None declared, Alberto Cavazza: None declared, Maria Grazia Catanoso: None declared, Pierluigi Macchioni: None declared, Lucia Spaggiari: None declared, Luca Cimino: None declared, Raffaella Aldigeri: None declared, Nicolò Pipitone: None declared, Antonio Fontana: None declared, Massimiliano Csaali: None declared, Stefania Croci: None declared, Nicolò Girolimetto: None declared, Carlo Salvarani Grant/research support from: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis, Consultant of: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis

Objective To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls. Methods All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls. Results 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter. Conclusions Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.

Objectives To evaluate aortic diameter and predictors of aortic dilatation using FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls. Methods All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study of each patient was independently evaluated by a radiologist and a nuclear medicine physician. The diameter of the aorta was measured at 3 different levels: ascending, descending thoracic and infrarenal aorta. Aortic dilation was defined as a diameter of >4 cm in the ascending,≥4 cm in the descending thoracic and ≥3 cm in the infrarenal aorta. Aortic FDG uptake was graded at the same levels using a 0–3 semiquantitative scale and was reported as negative (score 0 or 1) or positive (score 2 and 3). Patients younger than 50 years at symptoms’ onset were classified as Takayasu arteritis (TAK), while those older than 50 years as giant cell arteritis (GCA). 29 age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT in the same time interval without evidence of aortic FDG uptake were selected as controls. Results 93 patients with LVV were included in the study. 53% of patients were newly-diagnosed; the remaining 47% had a median disease duration of 34 months. At first PET/CT, the mean (SD) diameter of descending thoracic aorta was significantly higher in LVV patients compared with controls [28.07 (4.40) vs 25.60 (3.59) mm, p=0.012]. At last PET/CT, after a median time of 31 months, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p=0.029] and descending thoracic aorta [28.42 (4.82) vs 25.72 (3.55) mm, p=0.007] and more frequently had aortic dilatation [19% vs 3%, p=0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p=0.001], and the diameter of ascending [OR 2.03, p According to age at symptoms onset, 56% of patients were classified as GCA and 44% as TAK. Compared with TAK, GCA patients had higher aortic diameter at all 3 levels evaluated in both first and last PET/CT study. However there were no differences in the proportion of patients with aortic dilatation (at last PET/CT 23% in GCA vs 15% in TAK, p=0.306). The results remained unchanged when the analysis were restricted to the newly-diagnosed patients. Conclusions Patients with large vessel vasculitis are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and aortic diameter at first imaging study. Positive aortic FDG uptake at first PET/CT is not associated with increased risk of aortic dilatation. Disclosure of Interest None declared

Aim Erdheim-Chester disease represents a clonal systemic proliferation of histiocytes. Bone is the most common site of involvement, although almost any organ, including the lungs, can be affected. Methods and results The diagnosis of Erdheim-Chester disease can be difficult, owing to its rarity and protean presentation. Correlation between clinical, radiological and histological findings is mandatory for identification of the disease. Foamy histiocytes, lacking Langerhans cell markers, represent the typical histological findings, although their absence does not rule out Erdheim-Chester disease. Identification of BRAF mutation can be helpful in making the diagnosis, and allows for the development and application of targeted therapies in this setting. Conclusions Herein, we describe two cases presenting with lung involvement and vertebral lesions, lacking the more typical long-bone involvement. One case histologically mimicked Rosai-Dorfman disease. However, both cases harboured the pathognomonic BRAFV600E mutation.

With advances in our understanding of the pathogenesis of large vessel vasculitides, we recognise the persistence of inflammation in large vessels, sometimes despite therapy to control clinical symptoms. Achieving an early diagnosis and establishing the extent of disease are important steps in improving our management of these diseases. Imaging is playing an increasing role in the assessment of these patients from diagnosis to prognosis. We review the current and potential role of two important and potentially complementary imaging techniques of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in the evaluation of patients with giant cell arteritis and Takayasu arteritis.

Objective Chronic periaortitis (CP) usually responds to glucocorticoids, but some patients have glucocorticoid-refractory disease or contraindications to glucocorticoid therapy. This study was undertaken to evaluate treatment with the anti–interleukin-6 receptor (anti–IL-6R) antibody tocilizumab in 2 patients with CP, one with refractory disease and the other with contraindications to glucocorticoids, and to assess IL-6 levels in an additional cohort of patients with CP. Methods Both patients were given intravenous tocilizumab (8 mg/kg) once every 4 weeks for 6 months. Serum IL-6 was measured in 22 patients with active CP and 16 healthy controls. Tissue IL-6 expression was assessed by confocal microscopy in biopsy specimens obtained from 6 patients with CP. Results In the first patient, whose disease was refractory to various immunosuppressive treatments, tocilizumab added to ongoing therapy with prednisone and methotrexate allowed prednisone withdrawal and induced resolution of symptoms, acute-phase reactant normalization, and reduction in 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography. The patient experienced a relapse 7 months later and was successfully retreated with tocilizumab. In the second patient, who was unable to tolerate glucocorticoids because of psychiatric side effects, tocilizumab monotherapy induced sustained clinical and laboratory remission, 18F-FDG uptake disappearance, and CP shrinkage. Serum IL-6 levels were significantly higher in patients with active CP than in controls (P < 0.0001), and IL-6 was abundantly expressed in biopsy specimens from CP patients, particularly by T cells, B cells, histiocytes, fibroblasts, and vascular smooth muscle cells. Conclusion Tocilizumab may be a therapeutic option for CP. The systemic and tissue up-regulation of IL-6 in CP, together with the clinical benefit of IL-6R blockade observed in our 2 patients, suggest that IL-6 may contribute to CP pathogenesis.

We report a new case of ectopic Cushing’s syndrome caused by an ACTH-producing pheochromocytoma. A 55-year-old woman presented with a history of severe proximal muscle weakness, polyuria, progressive virilization, anxiety, dyspnea on exercise, difficult to treat hypertension, and type 2 diabetes mellitus since 4 months. The laboratory data demonstrated ACTH-dependent hypercortisolism. The abdominal computed tomography scan showed a 30 mm well-defined mass in the left adrenal gland suggestive for pheochromocytoma. The adrenal veins were sampled, with intraprocedural cortisol measurement, to dosing selective ACTH and cathecolamines. The results established clearly the left adrenal gland as the source of ACTH overproduction. A left sided adrenalectomy was performed with subsequent resolution of Cushing’s syndrome. The patient was discharged in good clinical condition.

The pathologist is frequently involved in the diagnostic approach to the patient with suspected sarcoidosis. Although the histologic diagnosis is generally not difficult, atypical and underrecognized features may occasionally occur and may result in diagnostic problems. The authors review the histology of pulmonary sarcoidosis, focusing particularly on these unusual problematic findings.

A 76-year-old man, non-smoker, former bricklayer, was admitted to the Infectious Diseases Unit for cough and mild fever persisting for more than 1 month. The patient had no other significant medical problems and had not recently travelled abroad. There were no significant findings on physical examination. Biochemical examinations showed an increase in inflammatory markers (CRP 7.9 mg/dl) and neutrophilic leukocytosis (14×109/l). Quantiferon test was negative, as were the autoimmune and the oncological markers. Nodular opacities were seen in both lungs on chest x-ray, and a subsequent CT scan showed multiple nodules located in all areas, but particularly in the subpleural location. Some of these nodules had features of cavitation. No ground-glass opacities were present (figure 1A). Mediastinal lymph nodes were slightly enlarged with a maximum diameter of 20 mm. Two ultrasound-guided percutaneous biopsies of the peripheral subpleural nodules were performed, with histological evidence of a suppurative inflammatory infiltrate with negative culture results. A bronchoscopy with bronchoalveolar lavage and transbronchial biopsy showed an intra-alveolar proteinaceous material and no microorganisms (figure 1B); microbiological cultures …

SummaryThe diagnosis of idiopathic pulmonary fibrosis (IPF) currently requires an integrated clinical–radiological–pathological approach in which the histology plays a different role from in the past. The first reason for this change is that non-invasive diagnostic procedures, particularly pulmonary function tests and high resolution computed tomography, have become increasingly competitive with biopsy in providing prognostic information. The other reason is a better appreciation of the limitations of histology: sampling error and interobserver variation. In this review we analyze the reasons for this change of perspective, provide an update on the practical role of histology in the diagnosis of IPF and discuss some of its complications.

Sir,Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune disease characterised by granulomatous destruction of intrahepatic bile ducts. Extrahepatic manifestations are frequent and in...

Mucosa-associated lymphoid tissue (MALT) lymphomas were first described by Isaacson and Wright in 1983 in a small series of patients with low-grade B-cell gastrointestinal lymphomas. Although MALT lymphomas occur most frequently in the stomach, they have also been described in various non-gastrointestinal sites, such as the salivary gland, conjunctiva, thyroid, orbit, lung, breast, kidney, skin, liver, uterus, and prostate. The risk of a diagnostic dilemma is reduced by the favorable prognosis of this low-grade lymphoma and its tendency to remain localized to the primary site for a long time. On therapeutic grounds, in contrast to nodal lymphomas, low-grade MALT lymphomas also respond favorably to local treatments, such as surgery and/or local radiation therapy. The outcome and prognosis of low-grade MALT lymphomas are more favorable than those for other extranodal lymphomas. The purpose of this review is to point out the state of the art regarding bronchus-associated lymphoid tissues lymphomas in terms of etiology, pathogenesis, clinics, and therapeutics, including our single-center experience of 23 cases.

Background MRI is widely used to evaluate muscle inflammation in myositis. Muscle edema on STIR sequences is thought to reflect active inflammation. However, it is unclear how useful MRI is in following up patients with myositis, in particular which is its sensitivity to change after treatment onset or intensification. Objectives To assess changes in MRI muscle edema and to correlate MRI edema score with serum creakine kinase (CK) and muscle strength in a cohort of patients with myositis at their first presentation to our centers (T0) and at follow-up after onset/intensification of immunosuppressive therapy (T1). Methods We enrolled in 2 Rheumatology centers 36 patients, 17 with dermatomyositis (DM) and 19 with polymyositis (PM) diagnosed according to Bohan and Peter criteria. In all patients, CK was measured, manual muscle test (MMT) was performed and MRI sequences were acquired within a week. MRI edema (1= present, 0= absent) was assessed bilaterally in 17 thigh and pelvic floor muscles. An MRI composite edema score (0-17) was calculated by adding the separate scores bilaterally and dividing them by two as described elsewhere (1). The CK upper limit of normal was 190 U/l. The (single measures) intraclass correlation coefficient (ICC) between the Radiologists involved was 0.78. Muscle strength was measured by MMT and graded according to the Medical Research Council extended scale (0-5). The ICC between the 2 physicians performing the MMT was 0.8. Analysis was performed by Wilcoxon sum rank and Spearman9s tests, as appropriate. Results Mean age (years ± SD) was 54±15. The ratio F:M was 31:5. MRI was positive (edema score ≥1) in 26 (72%) patients at T0 and in 18 (50%) at T1. Mean MRI edema score was 5±5.2 (mean ± SD) at T0 and 2.4±4.5 at T1 (p=0.002). Median and interquartile range (IQR) of MRI edema score were 3.5 (8) at T0 and 0.5 (4.5) at T1. CK was elevated in 22 (61%) patients at T0 and 10 (28%) at T1. CK was 1,816±3,560 at T0 and 531±1,536 at T1 (p=0.002). MMT score was 4.4±0.44 at T0 and 4.6±0.40 at T1 (p=0.02). MRI edema score did not correlate with CK or MMT scores neither at T0 nor T1. Eleven patients had a normal CK but a positive MRI at T0. In 5 of these patients, MRI became negative at T1. In the 11 patients with a normal CK but positive MRI at baseline, MRI edema score decreased from 6.7±5.3 at T0 to 2.4±2.7 at T1 (significance not calculated because of the small sample size). Conclusions MRI is a useful tool to monitor patients with myositis, and might particularly have a role in monitoring disease activity in patients with a normal serum CK at baseline. Larger studies are required to confirm our findings. The last 2 authors share senior authorship References Clin Exp Rheumatol 2012; 30:570-3 Disclosure of Interest None declared

Background MRI is widely used to evaluate muscle inflammation in myositis. Muscle edema on STIR MRI sequences is thought to reflect active inflammation. However, it is unclear whether MRI has an added value over the cheaper measurement of serum creatine kinase (sCK) levels. Objectives To assess the concordance between sCK and MRI edema in a cohort of patients with myositis at their first presentation to our centers. Methods We enrolled in 2 Rheumatology centers 73 patients, 34 with dermatomyositis (DM) and 39 with polymyositis (PM) diagnosed according to Bohan and Peter criteria. 33% of patients were untreated. In all patients, sCK were measured and MRI sequences were acquired at the same time. MRI edema (1= present, 0= absent) was assessed bilaterally in 17 thigh and pelvic floor muscles. An MRI composite edema score (0-17) was calculated by adding the separate scores bilaterally and dividing them by two as described elsewhere (1). sCK was considered positive if values were above the upper limit of normal (190 U/l), while MRI was considered positive if the edema score was at least 1. The (single measures) intraclass correlation coefficient (ICC) between the Radiologists involved was 0.78. Muscle strength was measured by MMT (manual muscle testing) and graded according to the Medical Research Council extended scale (0-5). The ICC between the 2 physicians performing the MMT was 0.8. Results sCK and MRI were discordant in 47% of patients with myositis, more frequently in DM (59%) than in PM (39%). 56% of patients with DM, but only 15% of those with PM had a positive MRI with normal sCK. There was a significant correlation between MRI score and muscle strength of the hip flexors (Spearman9s rho 0.26, p 0.028) but not between MRI score and overall muscle strength. MRI scores did not correlate with sCK. No significant differences were found between treated and untreated patients for any study variable (Mann-Whitney test, p>0.05). Conclusions MRI is a useful tool to assess disease activity in myositis, especially in DM, where it can be identify a sizeable number of patients who have normal sCK. Further studies of larger cohorts are warranted to confirm our findings. References Clin Exp Rheumatol 2012; 30:570-3 Disclosure of Interest None declared

Background MRI is often used to assess muscle inflammation in myositis. Muscle edema on short tau inversion recovery (STIR) sequences is thought to represent active inflammation. Dermatomyositis (DM) and polymyositis (PM) affect very frequently thigh muscles. However, it is unknown whether DM and PM differ in the respective involvement of the various thigh muscle groups. Objectives To assess which thigh muscle groups are preferentially affected by DM and PM, respectively Methods We analysed 72 patients from 2 Rheumatology centers, 31 with DM and 41 with PM diagnosed according to Bohan and Peter criteria. MRI edema (1= present, 0= absent) was assessed bilaterally on STIR sequences in 17 thigh/pelvic floor muscles. An MRI composite edema score (0-17) was calculated by adding the separate scores bilaterally and dividing them by two as described elsewhere (1). The (single measures) intraclass correlation coefficient (ICC) between the Radiologists involved was 0.78. Fisher9s exact test was used for comparison of binomial data. Results Age (years, mean ± SD) was similar in patients with DM (53±16) and PM (56±16). The F:M ratio was similar in DM (23/8) and PM (32/9). Disease duration (months, mean ± SD) was longer (20±31) in DM than in PM (52±68) (p=0.02). The frequency of the thigh muscle groups involved in DM and PM is shown in the Table below. Conclusions Compared with PM, DM affects more frequently some muscle groups. Posterior muscle groups appear to discriminate poorly between DM and PM. These findings may be useful for differential diagnostic purposes in patients with histological features of DM without the typical skin rash as well as to target physiotherapy on more frequently affected muscles. Larger studies are needed to confirm our preliminary findings. The last 2 authors share senior authorship. References Clin Exp Rheumatol 2012; 30:570-3. Disclosure of Interest None declared

Objectives Glucocorticoids (GCs) are the most used drugs for the treatment of idiopathic retroperitoneal fibrosis (IRF).Several steroid-sparing agents, including immunodepressants and tamoxifen, have been used with varying success. However, some patients are resistant to these therapies and valuable medical treatments are not available.The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with IRF. Methods Two patients received monthly TCZ infusions (8 mg/kg bodyweight) for six consecutive months.One of the patients treated with TCZ was previously unsuccessfully treated with IFX and abatacept and one patient was naive to biological agents.Disease activity and drug tolerability were assessed every month clinically and by laboratory tests such as ESR, CRP, IL-6, and the IL-6 soluble receptor (sIL-6R).18F-fluorodeoxyglucose PET (PET/CT) and abdominal Compurerized Tomography(CT)-scans were used for monitoring disease activity and treatment response. Results All two patients had a satisfactory clinical and laboratory response with a significant improvement of CT and PET findings.A reduction of retroperitoneal mass greater than 25% was observed in all patients. Remission maintenance therapy with MTX (20 mg/weekly)was started in all two patients. No serious adverse events were noted Conclusions TCZ is potentially effective treatments for patients with IRF that warrants evaluation in randomized trials. Disclosure of Interest None Declared

Background Right-to-left shunt (RLS) may be the cause of marked hypoxemia, a respiratory insufficiency which is usually difficult to diagnose by respiratory physicians as it develops in the absence of an intrinsic lung disease. Case presentation We report a case of RLS in a patient with a hepatopulmonary syndrome caused by chronic autoimmune cholangitis. RLS was suspected clinically by physical examination and by standard CT imaging and MIP reconstruction of the pulmonary vascular bed. Repeated previous transthoracic echocardiography (TTE) studies did not reveal shunts or any cardiac defect. The final diagnosis was made by means of a minimally invasive transcranial Doppler examination with the use of saline agitated with 0.5 ml of patient’s blood as contrast solution. Conclusions Transcranial Colour-Coded Duplex Sonography (TCCS) with saline contrast medium injection is described to have a higher sensitivity than TTE and comparable to transesophageal echocardiography (TEE) in RLS diagnosis. The collaboration of neurologists in diagnosing respiratory insufficiency is very important as the examination is simple, well tolerated in comparison with the discomfort associated with transesophageal echocardiography, and minimally invasive in comparison with angiography, which is the last diagnostic procedure in this clinical scenario. In order to confirm RLS, TCCS with blood-saline contrast medium injection should be performed for the diagnosis of chronic hypoxemia for which causes are not detected with routine clinical examinations.