Comparison of salivary gland MRI and ultrasonography findings among patients with Sjögren's syndrome over a wide age range.

OBJECTIVES: This retrospective study compared MRI and US findings among patients with SS over a wide age range. METHODS: Ninety patients with SS aged 8-84 years who had undergone both MRI and US examinations were divided into four groups according to age, as follows: <18 years (juvenile SS, JSS), 9 patients; 18-39 years, 12 patients; 40-69 years, 53 patients; >69 years, 16 patients. Imaging findings of parotid glands (PGs) and submandibular glands (SMGs) were compared among the four groups. Furthermore, the relationships within and between imaging findings and various clinical findings were examined. RESULTS: On MRI, patients with JSS commonly exhibited multiple high-intensity spots in the PGs on MR sialography and fat-suppressed T2-weighted imaging. With increasing SS group age, the frequencies and numbers of the high-intensity spots were lower. Fat areas on MRI and hyperechoic bands on US were rarely observed in the PGs and SMGs of patients with JSS, whereas they were more common in patients with adult SS. In addition, the presence of hyperechoic bands on US, the presence of fat areas on MRI, and decreased salivary flow were associated with one another. CONCLUSION: Salivary gland imaging findings in patients with JSS were characterized by punctate sialectasis, whereas those findings in patients with adult SS were characterized by fatty degeneration. Distinct findings in patients with JSS and adult SS are likely to reflect differences in glandular lesion stage. MRI and US are presumably useful for evaluation of glandular lesion severity during follow-up.

Imaging findings and treatment outcomes of a rare subtype of medication-related osteonecrosis of the jaw.

INTRODUCTION: In our previous study, we found a rare type of medication-related osteonecrosis of the jaw (MRONJ), which shows periosteal reaction (PR) at a site distant from osteolytic lesions or the extraction site (periosteal reaction dominant type, PRd type), even though the osteolytic lesions in the bone marrow are localized. The causes and treatment of MRONJ remain unclear; hence, this study aimed to describe the imaging and clinical features of the PRd type. MATERIALS AND METHODS: MRONJ patients who visited Nagasaki University Hospital between 2009 and 2020 and received conservative therapy as initial treatment were included in this study. The PR site, imaging findings, initial symptoms, outcome, and time to progression were examined. RESULTS: Among 59 MRONJ patients treated with conservative therapy, 38 did not show PR (PR- type), 15 showed PR near the osteolytic region (PR + type), and 6 had the PRd type. All patients with the PRd type had submental abscesses, and computed tomography (CT) images demonstrated PR on the lingual side of the anterior mandible. Osteolytic lesions progressed in 6/6 PRd type (100%), 5/15 PR + type (33.3%), and 2/38 PR- type (5.3%) patients. Time to progression for the osteolytic region on CT was short for the PRd type, at 56-148 days (median 79 days). CONCLUSION: Among the MRONJ types, the PRd type has a poor prognosis. Therefore, accumulating and analyzing more PRd cases in the future is warranted. This is the first report to describe the presence of this specific subtype of MRONJ.

Periosteal reaction of medication-related osteonecrosis of the jaw (MRONJ): clinical significance and changes during conservative therapy.

PURPOSE: We previously reported that the periosteal reaction (PR) in medication-related osteonecrosis of the jaw (MRONJ) is a poor prognostic factor in surgical cases, but it is not clear how PR changes during conservative therapy. The purpose of this retrospective study was to compare computed tomography (CT) findings at the first visit and during follow-up visits in MRONJ patients subjected to conservative therapy and to investigate factors associated with the exacerbation of PR during conservative therapy. METHODS: Sixteen patients with MRONJ of the lower jaw who underwent conservative therapy and experienced a PR on CT images at the first visit and underwent CT examination again after 6 months or more were enrolled in the study. Clinical features and CT findings (extent of osteolytic lesion, extent of PR, type of PR, and changes during conservative treatment) were investigated. RESULTS: On the second CT scan, the osteolytic lesion improved in 4 patients, had not changed in 5, and deteriorated in 7, whereas the PR improved in 5 patients, had not changed in 4, and deteriorated in 7 patients. PR was significantly deteriorated in patients who continued to receive antiresorptive agents during conservative treatment and in patients with deteriorated osteolytic lesions. CONCLUSION: PR in MRONJ often expands during conservative therapy and the PR type progresses from the attached type to the gap type, and the irregular type, but discontinuation of antiresorptive agent may improve PR as well as osteolytic lesions.

Salivary gland ultrasonography as a primary imaging tool for predicting efficacy of xerostomia treatment in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate ultrasonography (US) grading of salivary gland disease as a predictor of treatment efficacy for impaired salivary function in xerostomia patients with or without Sjögren's syndrome (SS). METHODS: We retrospectively analysed the prognostic importance of salivary US grading in 317 patients (168 with SS and 149 without SS). US images of the parotid and submandibular glands in each patient were individually categorized into grades 0-4 based on the extent of damage to the gland; and the sum total grade of the two gland types on either side was assigned a US score of 0-8 for each patient. The relative importance of US score and demographic and clinical variables was assessed using stepwise multiple regression analysis after various durations of xerostomia treatment. RESULTS: Multiple regression analysis indicated that the baseline US score before treatment was the most important factor [standardized regression coefficient (ß) = -0.523, t-statistic (t) = -7.967, P < 0.001] in predicting negative outcomes in SS patients. Treatment duration (ß = 0.277, t = 4.225, P < 0.001) was also a significant but less important positive variable. On the other hand, US grading did not effectively predict treatment outcomes in non-SS patients, with treatment duration (ß = 0.199, t = 2.486, P = 0.014) and baseline salivary flow rate before treatment (ß = -0.172, t = -2.159, P = 0.032) being significant but weak predictors of positive and negative outcome, respectively. CONCLUSION: Salivary gland US grading may help to predict outcomes of treatment for impaired salivary function in patients with SS.

Reevaluation for clinical manifestations of HTLV-I-seropositive patients with Sjögren's syndrome.

BACKGROUND: The aim of the study was to reassess the prevalence and characteristics of human T lymphotropic virus type I (HTLV-I)-associated Sjögren's syndrome (SS) and SS in HTLV-I-associated myelopathy (HAM) based on the American European Consensus Group (AECG) criteria in HTLV-I endemic area, Nagasaki prefecture. METHODS: The 349 patients who underwent a minor salivary gland biopsy (MSGB) for suspected SS were retrospectively classified by AECG classification criteria and divided with or without anti-HTLV-I antibody. RESULTS: The HTLV-I data-available 294 patients were investigated. One hundred-seventy patients were classified as SS and 26.5 % were HTLV-I-seropositive. We have included 26 patients with HTLV-I-associated myelopathy (HAM) and 38.5 % were classified as having SS. The prevalences of ANA and anti-SS-A/Ro antibody of HAM + SS were significantly low compared to the HTLV-I asymptomatic carriers (AC) with SS and the HTLV-I-seronegative SS patients, although lacrimal dysfunction tended to be high in HAM + SS and significantly high in AC + SS patients compared with the patients with HTLV-I-seronegative SS. The focus scores of MSGB in the HAM + SS patients were similar to those of the AC + SS patients and the HTLV-I-seronegative patients with SS. Among the MSGB-positive patients, there was a low prevalence of ANA in the HAM + SS patients. Similar results were obtained in case of anti-SS-A/Ro or SS-B/La antibody. CONCLUSION: In HTLV-I endemic area, high prevalence of anti-HTLV-I antibody among SS as well as the characteristics of HAM + SS and AC + SS was still determined by AECG classification criteria.

Comorbid case of IgG4-related disease and primary Sjögren's syndrome.

A 63-year-old man with enlargement of the bilateral submandibular glands visited with elevated serum IgG4. A biopsy specimen showed plasma cell infiltration with more than 50% IgG4/IgG staining, suggesting the existence of IgG4-related disease (IgG4-RD). Positive anti-SS-A/Ro antibody and the labial salivary gland's biopsy suggested existence of primary Sjögren's syndrome (pSS). Administration of glucocorticoid improved the serum IgG4 level while reducing the submandibular gland lesions. Positive TUNEL staining suggested the coexistence of IgG4-RD and pSS.

Ultrasonography as an additional item in the American College of Rheumatology classification of Sjögren's syndrome.

OBJECTIVE: In this study we evaluated US as an additional classification item in the ACR classification of SS. METHODS: Of 581 patients classified as either SS (n = 364) or non-SS (n = 217) based on the minimum requirements of the American-European Consensus Group (AECG) classification, 184 patients (102 SS and 82 non-SS) who had scored two or more positive or two or more negative results according to the ACR criteria were selected. The AECG classification was used as the gold standard. A parotid and/or submandibular gland that was assigned a score ≥G1 was designated as SS positive. We evaluated US alone or with varying combinations of the ACR classification items in the diagnosis of SS. RESULTS: The ACR criteria diagnosed the 184 patients with 91% sensitivity, 90% specificity and 91% accuracy. US alone diagnosed the 184 ACR patients with 79% sensitivity, 90% specificity and 83% accuracy, which was comparable to the results of US diagnosis in the AECG cohort (81%, 86% and 83%, respectively). Incorporating the US criteria as an alternative to one of the three ACR classification items achieved 89-91% sensitivity, 87-96% specificity and 89% or 92% accuracy, which was comparable to that of the original ACR classification. Furthermore, kappa analysis indicated that the results of the original ACR and US-replaced ACR classifications matched completely (κ = 0.960-0.974). CONCLUSION: These results suggest that US can be used as an alternative to any of the three ACR classification items.

Anti-centromere antibody positivity is an independent variable associated with salivary gland ultrasonography score in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands. SS also exhibits extra-glandular manifestations and specific autoantibodies. Salivary gland ultrasonography (SGUS) is a common procedure used to assess the severity of glandular involvement. However, the association between SGUS and extra-glandular lesions remains poorly understood. This study aimed to identify clinical indices, including disease activity, associated with glandular involvement using SGUS in patients with SS. We included 115 patients with SS and 90 without SS. Patients with SS had significantly higher ultrasonography (US) score than patients without SS. Multivariate analysis revealed focus score, Saxon test positivity, and anti-centromere antibody (ACA) positivity as independent variables associated with the US score in patients with SS. In addition, these results were similar to those obtained in patients with primary SS. Patients with SS and ACA positivity had higher US score and an increased prevalence of hyperechoic bands in the parotid glands and submandibular glands. In conclusion, this study indicated that ACA positivity is associated with the US score in patients with SS. These results suggest that US findings in patients with ACA positivity might show specific changes in the salivary glands, especially fibrosis.

Metastatic Lymph Node Detection on Ultrasound Images Using YOLOv7 in Patients with Head and Neck Squamous Cell Carcinoma.

Ultrasonography is the preferred modality for detailed evaluation of enlarged lymph nodes (LNs) identified on computed tomography and/or magnetic resonance imaging, owing to its high spatial resolution. However, the diagnostic performance of ultrasonography depends on the examiner's expertise. To support the ultrasonographic diagnosis, we developed YOLOv7-based deep learning models for metastatic LN detection on ultrasonography and compared their detection performance with that of highly experienced radiologists and less experienced residents. We enrolled 462 B- and D-mode ultrasound images of 261 metastatic and 279 non-metastatic histopathologically confirmed LNs from 126 patients with head and neck squamous cell carcinoma. The YOLOv7-based B- and D-mode models were optimized using B- and D-mode training and validation images and their detection performance for metastatic LNs was evaluated using B- and D-mode testing images, respectively. The D-mode model's performance was comparable to that of radiologists and superior to that of residents' reading of D-mode images, whereas the B-mode model's performance was higher than that of residents but lower than that of radiologists on B-mode images. Thus, YOLOv7-based B- and D-mode models can assist less experienced residents in ultrasonographic diagnoses. The D-mode model could raise the diagnostic performance of residents to the same level as experienced radiologists.

IgG4-related Mikulicz's disease: ultrasonography of the salivary and lacrimal glands for monitoring the efficacy of corticosteroid therapy.

OBJECTIVES: IgG4-related Mikulicz's disease (IgG4-MD) has been recently established as a subtype of IgG4-related diseases involving the salivary and lacrimal glands, and the diseased glands are characteristically and highly responsive to corticosteroid therapy. We retrospectively evaluated ultrasonography (US) of the salivary and lacrimal glands for monitoring the efficacy of corticosteroid treatment in patients with IgG4-MD. METHODS: US features of the salivary and lacrimal glands were assessed and compared with the serum IgG4 levels in 8 patients with IgG4-MD before and at various stages after initiation of oral corticosteroids. RESULTS: US features of the lacrimal and salivary glands of patients with IgG4-MD were characterised by multiple hypoechoic areas in enlarged glands. The submandibular glands were most frequently involved by the disease, and bilateral glands of the same type were similarly affected exhibiting the same hypoechoic pattern. Alleviations of abnormal gland architecture and size in response to corticosteroid therapy were effectively detected with US. The US findings of the involved glands were proportional to the serum IgG4 level before and during the corticosteroid therapy. CONCLUSIONS: US helps monitor the efficacy of corticosteroid treatment in patients with IgG4-MD.

Three Signs to Help Detect Sjögren's Syndrome: Incidental Findings on Magnetic Resonance Imaging and Computed Tomography.

This study aimed to retrospectively investigate the prevalence of Sjögren's syndrome (SS) among patients with ranulas, parotid cysts, or parotid calcifications; identify the characteristic magnetic resonance imaging (MRI) or computed tomography (CT) findings of the lesions associated with SS; and compare the SS disease stages among SS patients with the three lesion types. A total of 228 patients with the lesions were classified into SS, possible SS, and non-SS groups. The prevalence of SS among patients with ranulas, parotid cysts, or parotid calcifications was 16%, 24%, and 40%, and the rates of either SS or possible SS were 25%, 41%, and 64%, respectively. SS was associated with (i) ranulas: ≤17 mm; (ii) parotid cysts: bilateral and multiple; and (iii) parotid calcifications: in females, bilateral, multiple, parenchymal, and no coexisting calcifications in other tissues. SS patients with ranulas were significantly younger and had lower submandibular gland stage scores on MRI/CT than those with other lesions. Additionally, in 58% and 15% of SS patients with ranulas and parotid calcifications, respectively, detection of the lesions led to the diagnosis of primary SS. Therefore, recognizing the prevalence of SS among patients with these lesions and the findings associated with SS can help detect undiagnosed SS.

A case of periosteal fasciitis located in the mandible in a child.

Periosteal fasciitis (PF), a subtype of nodular fasciitis, is an uncommon benign soft-tissue mass that originates from the periosteum or tissues adjacent to bones. PF has rarely seen in children, especially involving in the mandible. This case report presents a rare case of PF originating from the periosteum of the mandible in an 11-year-old girl. She was referred to our hospital with fast-growing painless swelling in her left mandible. Computed tomography revealed an exophytic juxtacortical mass eroding the lower part of the left mandible and lower mandibular cortex with a periosteal reaction. The mass showed low signal intensity on T1-weighted magnetic resonance imaging (MRI) and high signal intensity on T2-weighted MRI. The apparent diffusion coefficient (ADC) of the lesion found to be moderate. Dynamic contrast-enhanced MRI revealed a gradual increment pattern in the central region of the mass. On 18F-fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT), relatively high 18F-FDG uptake was observed on the early scan and the 18F-FDG uptake was declined on the delayed scan. The clinical and conventional radiological findings of the mass were suggestive of malignancy. However, the findings of ADC and dynamic MRI and dual-time-point FDG-PET/CT favored benign etiology over malignant etiology. Histological and immunohistochemical findings along with reactive ossification of the periosteum confirmed the diagnosis of PF. Currently, comprehensive examinations, such as clinical, imaging, and histopathological examinations, are recommended for the definitive diagnosis of PF, while MRI and dual-time-point FDG-PET/CT could have a potential usefulness to differentiate from malignancy.

Retrospective Analysis of Treatment Outcomes of Maxillary Sinusitis Associated with Medication-Related Osteonecrosis of the Jaw.

Although maxillary sinusitis often occurs in patients with medication-related osteonecrosis of the jaw (MRONJ) of the upper jaw, there have been few reports on the treatment and outcomes for maxillary sinusitis associated with maxillary MRONJ. This study aimed to retrospectively investigate the treatment outcomes of maxillary sinusitis in patients with MRONJ of the upper jaw. There were 34 patients diagnosed with maxillary MRONJ and sinusitis by preoperative computed tomography who underwent surgery in our institution between January 2011 and December 2019. Age, sex, primary disease, stage of MRONJ, class and administration period of an antiresorptive agent, corticosteroid administration, preoperative leukocyte count and serum albumin level, periosteal reaction, sinusitis grade, maxillary sinus surgical procedure, and treatment outcomes of MRONJ and sinusitis were examined. There were 7 male and 27 female patients (average age, 74.7 years). Complete healing of MRONJ was obtained in 29 of 34 patients (85.3%). Maxillary sinusitis resolved or improved in 21 patients (61.8%) but did not change or worsen in 13 patients (38.2%). We found that complete resection of necrotic bone with intraoperative irrigation of the maxillary sinus may provide good treatment outcomes for maxillary sinusitis associated with MRONJ, although our findings were not statistically significant owing to the small number of patients.

Relationship between drug holiday of the antiresorptive agents and surgical outcome of medication-related osteonecrosis of the jaw in osteoporosis patients.

A drug holiday of 3 months does not promote separation of sequestra and is not correlated with treatment outcomes after surgical therapy in osteoporosis patients who receive antiresorptive agents and who have medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents alone or in combination with immune modulators or antiangiogenic medications, in the absence of radiation exposure to the head and neck region. The effectiveness of surgical treatment for MRONJ has been reported, but the timing of the operation remains controversial. The purpose of this study was to clarify whether preoperative drug holidays of antiresorptive agents promote sequestrum separation and improve treatment outcomes in patients who receive low doses of antiresorptive agents. This retrospective study included 173 patients who received low-dose antiresorptive agents and underwent surgical therapy. The effects of a drug holiday on the separation of sequestra and treatment outcomes were analyzed using logistic and Cox regression analyses. Multivariate analysis revealed that administration of an antiresorptive agent for more than 4 years, a high number of lymphocytes, and an extensive osteolytic area were significantly correlated with separation of sequestra, but drug holiday did not promote sequestrum separation. Furthermore, a drug holiday of 90, 120 or 180 days did not show any improvement in treatment outcomes. The drug holiday of the antiresorptive agents for the treatment of MRONJ is unnecessary, and surgical therapy should be performed early.

Relationship between Drug Holidays of Antiresorptive Agents and Surgical Outcomes in Cancer Patients with Medication-Related Osteonecrosis of the Jaw.

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients' age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients' surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.

Juvenile primary Sjögren's syndrome with ranula: is ranula a clinical sign that leads to early detection of Sjögren's syndrome?

Juvenile primary Sjögren's syndrome (pSS) is rare. Although recurrent parotitis is reported to be the most common symptom of juvenile pSS, the clinical symptoms and features of the syndrome are not well understood and are poorly defined. Here we report a rare case of juvenile pSS in a patient with plunging ranula. The patient had no symptoms other than swelling of the oral floor and had no symptoms of parotitis. Magnetic resonance imaging (MRI) revealed the diagnosis of plunging ranula. In addition, the findings of the bilateral parotid glands on MRI and subsequent ultrasonography (US) strongly suggested SS. On the basis of these imaging findings and laboratory data, a pediatric rheumatologist confirmed the diagnosis of juvenile pSS. The ranula may be one clinical sign of SS. However, this association remains generally unknown. Hypothesizing that SS might cause ranula development, we retrospectively investigated cases of patients with ranula who underwent MRI at our hospital. We found that many of these patients (> 20%) had characteristic findings strongly suggestive of SS. This result suggests that SS-induced changes in the sublingual glands are one cause of ranula formation. We think that ranula is a sign of early-stage SS. Therefore, patients with ranulae, whether adults or children, should undergo careful assessment of not only the sublingual glands but also the parotid and submandibular glands with MRI and/or US to investigate possible SS. This assessment may lead to early detection of SS.

Salivary gland ultrasonography: can it be an alternative to sialography as an imaging modality for Sjogren's syndrome?

OBJECTIVES: Salivary ultrasonography (US) was evaluated as an alternative imaging modality to sialography for Sjögren's syndrome (SS). METHODS: Parotid sialography and parotid and submandibular US were performed in 360 patients (188 with SS and 172 non-SS) who were suspected of SS and had fulfilled the American-European criteria (AEC) for SS or had received > or =3 of the objective examinations that were considered minimal requirements for classifying non-SS and had undergone both the imaging examinations. The glands were considered positive for SS if they exhibited peripheral sialoectatic changes on sialography and/or hypoechoic areas, echogenic streaks and/or irregular gland margins on US. The images obtained were independently rated as SS-positive or SS-negative by three radiologists in a blind fashion and the final decision was made by consensus. Interobserver and intermodality agreement was evaluated using kappa values for sialography and parotid and/or submandibular US. RESULTS: Average kappa values for the interobserver agreement were 0.81, 0.80 and 0.82 in sialography, parotid and submandibular US, respectively, indicating very good or good agreement. The kappa value for intermodality agreement between sialography and parotid US was 0.81 and between sialography and submandibular US was 0.76, indicating very good and good agreement, respectively. The diagnostic ability of parotid US was significantly lower than that of sialography (p<0.001, McNemar test). However, the diagnostic ability of submandibular US was comparable to that of sialography (p=0.153). CONCLUSIONS: Submandibular US is a promising technique that can be used as a practical alternative to sialography in the classification of SS.

A single centre retrospective analysis of AECG classification criteria for primary Sjogren's syndrome based on 112 minor salivary gland biopsies in a Japanese population.

OBJECTIVE: To assess the usefulness and performance of the American European Consensus Group (AECG) criteria based on minor salivary gland biopsy (MSGB) in Japanese patients with primary SS. METHODS: Among 208 MSGB cases, we retrospectively selected 112 subjects who satisfied the complete set of AECG classification criteria. Of the 112 subjects studied, 63 primary SS patients and 49 non-SS group subjects were classified according to the AECG criteria. The contribution of subjective and objective components was statistically analysed. RESULTS: Sex, dry eye, Saxon test, Schirmer's test, anti-SSA/Ro antibody, MSGB grading and sialography statistically contributed to the diagnosis. Multiple logistic regression analysis showed that positive MSGB [odds ratio (OR) 105; 95% CI 13, 849), positive anti-SSA/Ro antibody (OR 96; 95% CI 10, 923), a positive Saxon test (OR 46; 95% CI, 6, 340) and the existence of dry eye (OR 8, 95% CI 2, 43) were associated with the diagnosis of primary SS. Among the components of the AECG criteria, MSGB and anti-SSA/Ro antibody were very strong contributors. Furthermore, the abnormal-finding positive rate in sialography significantly correlated with MSGB grading (P-value for trend = 0.0006), although other subjective and objective components were not associated with MSGB grading. CONCLUSION: The usefulness of the AECG criteria for Japanese primary SS patients was confirmed.