Clinical Characterization and Predictive Factors for Progression in a Cohort of Patients with Interstitial Lung Disease and Features of Autoimmunity: The Need for a Revision of IPAF Classification Criteria.

Background and Objectives: The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Diagnostic yield of axillary artery ultrasound in addition to temporal artery ultrasound for the diagnosis of giant cell arteritis.

OBJECTIVES: There are limited data on the additional diagnostic yield of axillary artery ultrasound (axUS) in addition to temporal artery ultrasound (tempUS) for the diagnosis of giant cell arteritis (GCA). METHODS: Retrospective study of consecutive patients with suspected GCA who underwent a standardized axUS and tempUS between 01/2015 and 03/2017. The diagnostic yield of axUS in addition to ultrasound of the temporal arteries with respect to the final clinical diagnosis was assessed, with a positive axUS defined as circumferential, hypoechogenic thickening of the far wall axillary artery intima media thickness (axIMT) ≥1.3 mm. A subgroup of patients underwent PET-CT within one week before or after the sonographic study. Separate analyses were performed regarding certain subgroups according to clinical presentation and to clinical pre-test probability for cranial GCA. RESULTS: Out of 228 patients, 92 received a final diagnosis of GCA. From the 92 patients with a final diagnosis of GCA, 50 (54.3%), 13 (14.1%) and 15 (16.3%) had a positive tempUS, positive axUS, and combined positive tempUS and axUS, respectively. The sensitivity of sonographic imaging for the final diagnosis of GCA increased from 69.6% to 84.8%, when axUS results were considered in addition to tempUS, while the specificity remained high (no false positive axUS). The diagnostic yield of axUS was highest in patients with a low clinical probability of cranial GCA and lowest in patients with symptoms of ocular ischemia. We observed a substantial rate (42.1%) of discordant results between axUS and PET-CT in a subgroup of 38 patients. CONCLUSIONS: In conclusion, axUS offers a substantial diagnostic yield in addition to tempUS in subjects with suspected GCA, mainly in those subjects with low clinical probability for cranial GCA.

Hyperechogenic intimal lesions and wall thickness of the temporal and facial arteries in elderly patients with arterial occlusions of the eye.

OBJECTIVE: To determine the association of arteriosclerosis, characterised by hyperechogenic intimal lesions (HIL), with wall thickness of the temporal and facial arteries in elderly patients with ocular arterial occlusions. METHODS: Patients suffering from non-arteritic ocular perfusion disorders were included. High-resolution compression sonography (18 MHz) images of the temporal arteries (frontal and parietal branch at the upper margin of the auricle) and facial arteries (at the crossing point of the artery over the mandible) were analysed for the presence of HIL (grade 0: absent; grade 1: moderate; grade 2: severe). Characteristics of patients with and without evidence of HIL >grade 1 were compared. RESULTS: In total, 330 cranial artery segments of 55 patients were analysed. HIL ≥grade 1 was present in 13.0% of all artery segments and in 38.1% of all patients. Patients with HIL ≥grade 1 in at least one arterial segment displayed significantly increased maximum wall thickness of the temporal arteries (0.62±0.23 mm vs 0.50±0.13 mm; p<0.01) and facial arteries (0.71±0.20 mm vs 0.54±0.19 mm; p=0.01). Patients with at least one temporal or facial artery segment with HIL were older, more often male and more frequently suffered from diabetes mellitus. CONCLUSION: The presence of HIL goes along with a significantly increased wall thickness of the temporal and facial arteries. These findings should be considered when interpreting the results of sonography of the cranial arteries in the diagnostic workup of suspected giant cell arteritis.

A Diagnostic Algorithm Based on a Simple Clinical Prediction Rule for the Diagnosis of Cranial Giant Cell Arteritis.

BACKGROUND: Risk stratification based on pre-test probability may improve the diagnostic accuracy of temporal artery high-resolution compression sonography (hrTCS) in the diagnostic workup of cranial giant cell arteritis (cGCA). METHODS: A logistic regression model with candidate items was derived from a cohort of patients with suspected cGCA (n = 87). The diagnostic accuracy of the model was tested in the derivation cohort and in an independent validation cohort (n = 114) by receiver operator characteristics (ROC) analysis. The clinical items were composed of a clinical prediction rule, integrated into a stepwise diagnostic algorithm together with C-reactive protein (CRP) values and hrTCS values. RESULTS: The model consisted of four clinical variables (age > 70, headache, jaw claudication, and anterior ischemic optic neuropathy). The diagnostic accuracy of the model for discrimination of patients with and without a final clinical diagnosis of cGCA was excellent in both cohorts (area under the curve (AUC) 0.96 and AUC 0.92, respectively). The diagnostic algorithm improved the positive predictive value of hrCTS substantially. Within the algorithm, 32.8% of patients (derivation cohort) and 49.1% (validation cohort) would not have been tested by hrTCS. None of these patients had a final diagnosis of cGCA. CONCLUSION: A diagnostic algorithm based on a clinical prediction rule improves the diagnostic accuracy of hrTCS.

Transocular sonography in acute arterial occlusions of the eye in elderly patients: Diagnostic value of the spot sign.

PURPOSE: To characterize the diagnostic yield of the spot sign in the diagnostic workup of acute arterial occlusions of the eye in elderly patients. METHODS: Clinical characteristics of consecutive patients aged ≥ 50 years with acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) or anterior ischemic optic neuropathy (AION) were recorded. Videos of transocular sonography were assessed for the presence of the spot sign by two blinded readers. Group comparisons were made between CRAO-patients with and without the spot sign. Two experienced cardiovascular physicians allocated CRAO-cases to a presumed aetiology, without and with knowledge on the presence/absence of the spot sign. RESULTS: One-hundred-twenty-three patients were included, 46 of whom suffered from CRAO. A spot sign was seen in 32 of 46 of patients with CRAO and in 7 of 23 patients with BRAO. Interobserver agreement was excellent (Cohen`s kappa 0.98). CRAO-patients with the spot sign significantly more frequently had a medical history of cardiovascular disease (62.8 vs. 21.4%, p = 0.03) and left heart valve pathologies (51.9 vs. 10%, p = 0.03). The spot sign was not found in any of the three patients with CRAO secondary to cranial giant cell arteritis. The assumed CRAO aetiology differed in 37% of cases between two cardiovascular physicians, regardless whether transocular sonography findings were known or not. CONCLUSION: The spot sign is a simple sonographic finding with excellent interobserver agreement, which proofs the embolic nature of CRAO, but does not allow exact attribution of the underlying aetiology.

Temporal artery compression sonography for the diagnosis of giant cell arteritis in elderly patients with acute ocular arterial occlusions.

OBJECTIVES: To validate cut-off values of quantitative high-resolution temporal artery compression sonography (TCS) for the diagnosis of cranial GCA (cGCA) in patients with acute arterial ocular occlusions and in an independent control group. METHODS: Consecutive patients who underwent TCS as part of the diagnostic workup of acute arterial ocular occlusions and controls not suffering from ocular ischaemia/systemic vasculitis were included. The diagnostic accuracy of the established TCS cut-off value of maximum temporal artery wall thickness (≥0.7 mm) and a novel numeric TCS score incorporating the degree of wall thickening in the four temporal artery segments assessed (0-3 points per segment) was tested by receiver operating characteristics analysis. Subgroup analyses were performed for female and male patients and patients older and younger than age of 70 years. RESULTS: Of 114 patients with acute ocular arterial occlusions, 30 patients received a final clinical diagnosis of cGCA. The sensitivity and specificity of the ≥0.7 mm TCS cut-off for the diagnosis of cGCA were 100 and 84.5% in the overall cohort. The TCS score did not improve the diagnostic yield (cut-off ≥5; sensitivity 100%, specificity 85.7%). In male patients >70 years of age, the specificity of TCS was limited, secondary to age- and sex-related differences in temporal artery wall thickness, which we confirmed in the independent control group. CONCLUSION: TCS yields high diagnostic accuracy in the diagnosis of cGCA in patients with acute ocular arterial occlusions. Age- and sex-related differences in temporal artery wall thickness influence the diagnostic accuracy of TCS.

Influence of carotid atherosclerotic plaques on pulse wave assessment with arterial tonometry.

OBJECTIVE: Aortic stiffness and central pressure measurements have become increasingly important for the overall estimation of cardiovascular risk. The aim of this study is to verify whether the presence of stenosis in the carotid arteries due to atherosclerotic plaques may induce a bias in the measurement of carotid-femoral pulse wave velocity (PWV) and in the analysis of central pulse waveform variables assessed by carotid tonometry. METHODS: Eighty-four patients (age: 67.1 ±â€Š12.4 years) undergoing screening for carotid atherosclerosis were enrolled, divided into three groups according to carotid ultrasound findings (NASCET criteria): 28 patients without significant stenosis, 30 patients with bilateral plaques, and 26 patients with right or left monolateral stenosis. PWV and other variables derived from the central pulse waveform analysis (central blood pressure, augmentation index and forward and backward waves) were measured at both right and left carotid arteries by a validated PulsePen tonometer. A repeatability study was performed in 28 young healthy patients (age: 25.4 ±â€Š2.9 years). RESULTS: A high degree of correlation was found between bilateral measurements in all groups, and particularly in groups with monolateral carotid stenosis, with no significant difference attributable to lateralized stenosis. Right-left differences in asymmetric groups were 0.35 ±â€Š5.12 mmHg (R = 0.960) for central blood pressure, -2.12 ±â€Š7.39% (R = 0.743) for augmentation index, 0.64 ±â€Š1.56 m/s (R = 0.947) for PWV, 0.08 ±â€Š8.48 mmHg for forward wave (R = 0.742) and 0.35 ±â€Š2.35 mmHg for backward wave (R = 0.907). CONCLUSION: Measurement of PWV and of variables derived from the central pulse waveform analysis by carotid tonometry is not biased by the presence of local atherosclerotic plaques.