Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Metavir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

Macrophage membrane-modified targeted phase-change nanoparticles for multimodal imaging of experimental autoimmune myocarditis.

Myocarditis is an important public health issue due to the high prevalence of sudden death in adolescents and young adults. Nevertheless, the early identification of myocarditis remains a serious problem for clinicians. There is no single non-invasive method to diagnose myocarditis in the currently available clinical guidelines and consensus. Molecular imaging is an effective approach for accurate diagnosis. Poly(lactic acid-glycolic acid) (PLGA) is considered to be the preferred carrier for molecular imaging because of its biosafety and modifiability. Macrophage membrane-modified biomimetic nanoprobes (MM-NPs) possess low immunogenicity and inflammation-directed chemotaxis capabilities and are repeatedly chosen as materials for targeted diagnosis and treatment of inflammatory diseases. In this study, experimental autoimmune myocarditis (EAM) was used as an animal model of inflammation. Previous studies have confirmed that this model is similar to pathological injury caused by acute myocarditis in humans. In multimodal imaging (US/PA/MRI), a phase-change material (PFH) and superparamagnetic iron oxide (SPIO) are used as imaging substances. Early identification of myocardial inflammatory sites was achieved by the tail vein injection of MM/NPs loaded with PFH and SPIO. This probe is expected to be a powerful tool for clinicians to diagnose myocarditis.

Radiological and histopathological features and treatment response by subtypes of interstitial pneumonia with autoimmune features: A prospective, multicentre cohort study.

BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

Imaging Features of Autoimmune Disease-Related Interstitial Lung Diseases.

Interstitial lung diseases (ILDs) associated with autoimmune diseases show characteristic signs of imaging. Radiologic signs are also used in the identification of ILDs with features suggestive of autoimmune disease that do not meet the criteria for a specific autoimmune disease. Radiologists play a key role in identifying these signs and assessing their relevance as part of multidisciplinary team discussions. A radiologist may be the first health care professional to pick up signs of autoimmune disease in a patient referred for assessment of ILD or with suspicion for ILD. Multidisciplinary team discussion of imaging findings observed during follow-up may inform a change in diagnosis or identify progression, with implications for a patient's treatment regimen. This article describes the imaging features of autoimmune disease-related ILDs and the role of radiologists in assessing their relevance.

Differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma using CT characteristics: a systematic review and meta-analysis.

OBJECTIVES: To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy. METHODS: A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model. RESULTS: A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7). CONCLUSION: Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate. CLINICAL RELEVANCE STATEMENT: This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement. KEY POINTS: • Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.

Differential Diagnosis of IgG4-related Pancreatitis and Pancreatic Cancer by MRI Features and Its Correlation with Serum IgG4 Level.

It was to analyze the diagnostic value of MRI in immunoglobulin G (IgG4)-related autoimmune pancreatitis (AIP) and pancreatic cancer (PC) and its relationship with serum IgG4 level. 35 patients with IgG4-related AIP (group A1) and 50 patients with PC (group A2) were enrolled. MRI was performed to determine serum IgG4 levels. Spearsman was used to analyze the relationship between MRI characteristics and serum IgG4 level. It was found that patients in group A1 showed double duct sign (DDS), pancreatic duct (PD) perforation sign, the proportion of main PD truncation, and main PD diameter/pancreatic parenchymal width ratio, which were different from those of patients in group A2 (P < 0.05). MRI had a sensitivity (Sen) of 88%, specificity (Spe) of 91.43%, accuracy (Acc) of 89.41%, positive predictive value (PPV) of 0.936, and negative predictive value(NPV) of 0.842 for the diagnosis of IgG4-related AIP and PC. Serum IgG4 levels were significantly negatively correlated with DDS and main PD truncation, significantly positively correlated with PD penetration sign, and extremely significantly negatively correlated with main PD diameter/pancreatic parenchymal width (P < 0.001). The results showed that MRI had high sensitivity and specificity for differentiating IgG4-related AIP from PC, and the diagnostic effect was good, which had a high correlation with serum IgG4 levels in patients.

Effect of maternal autoimmune diseases on fetal pulmonary artery Doppler indices: A case-control study.

OBJECTIVE: To compare the fetal pulmonary artery Doppler indices of pregnant women with autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and antiphospholipid syndrome (APS) with healthy pregnant women. METHODS: Thirty-nine pregnancies were included in the case group, 19 of them SLE, 12 with SS, and eight with APS. The gestational age-matched 54 healthy pregnant women were included in the control group. Peak systolic velocity, time-averaged velocity, systolic/diastolic ratio, pulsatility index, resistance index, acceleration time (AT), ejection time (ET), and AT/ET ratio were obtained from pulmonary artery waveform by using spectral Doppler ultrasound. RESULTS: Significantly shorter AT and lower AT/ET ratio were detected in the case group (p = < .001, p = < .001, respectively). The shortening of AT and decreasing of the AT/ET ratio were more predominant in the APS group. However, there was no significant difference between the SLE, SS, and APS groups in fetal pulmonary artery Doppler indices. Also, a moderate correlation was found between maternal disease duration (years) and fetal pulmonary artery AT (r = -.516, p = .001) and AT/ET ratio (r = -.558, p = < .001). CONCLUSION: Fetal pulmonary artery Doppler indices may be affected in maternal autoimmune diseases. Further studies are needed to evaluate fetal pulmonary Doppler indices such as AT and AT/ET ratio to predict neonatal respiratory morbidity and lung maturation in pregnant women with SLE, SS, and APS.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

Concomitant Pancreatic Ductal Adenocarcinoma and Type 1 Autoimmune Pancreatitis: A Potential Issue in the Diagnosis of Carcinoma by Endoscopic Ultrasound-guided Fine-needle Biopsy.

We herein report a 64-year-old man with concomitant pancreatic ductal adenocarcinoma (PDAC) and type 1 autoimmune pancreatitis (AIP). An endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from the pancreatic head mass revealed level 2 histology of AIP and atypical glands. We diagnosed definitive focal AIP using the clinical diagnostic criteria. Computed tomography revealed that the pancreatic mass had not been reduced by steroid therapy. Surgery was performed after a histological PDAC diagnosis was made via a transpapillary biliary biopsy. The resected specimen revealed PDAC associated with AIP. It is important to consider the cooccurrence of PDAC and AIP even if the histological diagnosis via an EUS-FNB is AIP.

Autoimmune Pancreatitis with Massive Ascites and Multiple Pancreatic Cysts Successfully Treated with Prednisolone.

A 64-year-old man with a history of diabetes and gallstones was admitted to our institution with suspected pancreatic malignancy. Computed tomography (CT) revealed multiple pancreatic cysts and massive ascites, and endoscopic ultrasonography (EUS) revealed a 28×27-mm hypoechoic mass in the pancreatic head. An EUS-guided fine-needle aspiration biopsy was performed, and there were no malignant findings. Based on the test results and imaging findings, type 1 autoimmune pancreatitis was suspected. The patient was administered 30 mg of prednisolone daily. After 11 days, CT revealed that the pancreatic cysts and ascites had reduced in size.

Progression and prognosis of interstitial pneumonia with autoimmune features: a longitudinal, prospective, multi-centre study.

OBJECTIVES: To evaluate the rate of progression towards specific autoimmune diseases (SADs) of a prospective, multi-centre cohort of patients classifiable as interstitial pneumonia with autoimmune features (IPAF). METHODS: IPAF patients were enrolled based on specific research criteria, and jointly followed by rheumatologists and pulmonologists for at least one year with clinical check-ups, serological exams including autoimmunity, capillaroscopy and high-resolution computed tomography (HRCT). Diagnostic assessment was repeated at least once a year, or earlier when deemed useful. RESULTS: We enrolled 191 IPAF patients through 95 different combinations of IPAF criteria. Of these, 24.1% progressed towards SAD, mainly in connective tissue diseases but also in microscopic polyangiitis. The IPAF patients who progressed were younger than stable IPAF patients (63±10 years vs. 68±9 years, p=0.002) and had a longer follow-up (36.9±18.7 vs. 29.3±15.7 months, p=0.007), but similar severity. No parameters were associated with overall progression, but some parameters were associated with the development of specific diagnoses: Sjögren's syndrome with positivity for SSA (p=0.007, χ2 7.4); idiopathic inflammatory myopathy with mechanic's hands (p=<0.0001, χ2 12.6), organizing pneumonia pattern (p=0.01, χ2 6.1), positivity for anti-Pm/scl (p=0.04 χ2 4.1) and anti-MDA5 (p=0.04, χ2 4.2); systemic sclerosis with palmar telangiectasias (p=<0.0001 2 18.3), positivity for anti-Scl70 (p=<0.0001 χ2 12.5) and anti-PM/Scl (p=0.001 χ2 10.1). CONCLUSIONS: IPAF patients had a rate of progression towards SAD similar to that reported in previous studies on undifferentiated connective tissue diseases, thus including some patients in which lung involvement could represent the first or even the sole clinical manifestation of a SAD.

Updated Role of High-frequency Ultrasound in Assessing Dermatological Manifestations in Autoimmune Skin Diseases.

Autoimmune skin diseases are a group of disorders that arise due to the dysregulated immune system attacking self-antigens, causing multiple tissue and organ lesions. With disease progression, the physical and psychological health of patients may be seriously damaged. High-frequency ultrasound is non-invasive, reproducible, and suitable for visualizing the fine structure of external organs. The usage of high-frequency ultrasound has increased in recent years in the auxiliary diagnosis and monitoring of various skin diseases; it serves as a promising tool for dermatological disease assessment. This review summarizes the characteristics of high-frequency ultrasound imaging in common autoimmune skin diseases, including systemic lupus erythematosus, scleroderma, psoriasis, dermatomyositis, and pemphigus/pemphigoid. The objective of this review is to provide new ideas and strategies for dermatologists to diagnose and track the prognosis of autoimmune skin diseases.

Analysis of Clinical, Serological, and Imaging Features of Autoimmune Pancreatitis and a Case-Control Study on Prognostic Factors in Response to Hormone Therapy.

Objective: The paper aimed to analyze the clinical, serological, and imaging features of autoimmune pancreatitis (AIP) and the prognostic factors affecting hormone therapy. Methods: A total of 106 patients with AIP enrolled in our hospital from March 2016 to August 2018 were treated with the hormone. The curative effect and recurrence were followed up. The patients were divided into relapse group (n = 42) and nonrelapse group (n = 64) according to the recurrence within 3 years after initial hormone therapy. The symptoms and signs, laboratory examination, and treatment were compared, and binary logistic regression was employed to explore the risk factors of AIP recurrence. Results: Among the 106 patients included in this study, there were 78 males and 28 females, with a male-to-female ratio of 3:1. The average age of onset was 56.25 ± 8.87 years; the minimum age was 39 years; and the maximum age was 7 years. The main clinical symptoms were jaundice (67.92%), abdominal pain (48.11%), and abdominal distension (33.96%). In addition, there were symptoms of weight loss, nausea, vomiting, itching, and gray stool. Previous complications included 27.35% diabetes (29/106), 22.64% hypertension (24/106), 35.84% smoking (38/106), and 28.30% alcohol consumption (30/106). The serological characteristics were mainly the increase in serum IgG4 level; 92.45% (98/106) level was higher compared to the upper limit of normal value; the median level was 11.65 g/L; and the highest level was 35.79 g/L. A total of 88.67% (94/106) had an abnormal liver function. The results of imaging examination indicated that 58.49% (62/106) of extrapancreatic organs were involved, of which 46.22% (49/106) were the most common bile duct involvement. All the patients in the group reached a state of remission after hormone treatment. After the disease was relieved, the patients were followed up for 3 years. The recurrence rate was 39.62% (42/106), and the median time of recurrence (month) was 9 (range 2-36). The recurrence rates within 1, 2, and 3 years were 20.75%, 31.13%, and 39.62%, respectively. Among the recurrent patients, 52.38% (22/42) relapsed within 1 year, 78.57% (33/42) within 2 years, and 100.00% (42/42) within 3 years. Multivariate analysis showed that the short duration of glucocorticoid therapy and involvement of extrapancreatic organs were risk factors for relapse after glucocorticoid therapy in patients with type I AIP. Conclusion: Type 1 AIP is more common in middle-aged and elderly men. The clinical symptoms of jaundice, abdominal pain, and abdominal distension are common, often accompanied by involvement of extrapancreatic organs, of which bile duct involvement is the most common. Type 1 AIP glucocorticoid treatment acceptance and disease remission are better, but the recurrence rate is higher after glucocorticoid treatment. Patients with a short time of glucocorticoid treatment and involvement of extrapancreatic organs may have a higher risk of recurrence.

IgG4-Related Disease: A Constellation of Abdominal Manifestations.

IgG4-related disease is an autoimmune condition that results in inflammation and fibrosis throughout multiple organ systems. This disease is rare; however, it can mimic many more prevalent conditions clinically and thus should be included in their differential diagnoses. Although autoimmune pancreatitis is the most common abdominal manifestation, the disease can afflict the hepatobiliary, vascular and renal systems as well. We present a case of a 78-year-old male with symptoms of chronic fatigue and weight loss. Imaging was performed with the expectation of revealing a malignancy, although the features of IgG4-related disease involving multiple organs were detected instead. Serology confirmed the diagnosis. It is imperative to diagnose IgG4-related disease early as it has a different treatment and favorable prognosis compared to many malignancies.