Ossifying fibrous epulis as an IgG4-related disease of the oral cavity: a case report and literature review

Background Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD. Case presentation A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy. Conclusions A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases

Background: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. Materials and Methods: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. Results: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. Conclusion: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

The effect of rose hip on experimental anti-GBM glomerulonephritis in systemic lupus erythematosus murine models

Background: Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease with ominous end organ manifestations significantly affecting the kidneys and joints. One of the most frequent manifestations is glomerulonephritis (GN), a renal disease distinguished by inflammation of the glomeruli that often leads to end stage kidney failure. Treatments often have severe side effects. Rose hip (RH) is derived from Rosa canina L. and has been used as a medicinal plant for centuries; it contains numerous beneficial constituents, and has the capacity to counter lipid peroxidation, oxidative stress, and inflammation. Methods: Nephritis was induced in 129/svJ strain mice using anti-glomerular basement membrane antibodies (anti-GBM). The experimental group was fed whole RH preparation (100mg/kg body weight per day) by oral gavage from D5 to D10; the control group was fed the diluent used to dissolve RH (10 mice per group). Mice were sacrificed on D11 and phenotyped for disease. Blood urea nitrogen (BUN) and proteinuria were measured; flow cytometry of kidneys was performed on both groups. Results: RH treatment decreased proteinuria, blood urea nitrogen, CD4+, CD8+, CD11b+Gr-1+ (neutrophil), and CD11b+CD11c+ (myeloid cells) compared with nephritis control. The presence of vitamin C was confirmed. RH largely maintained its total antioxidant capacity and some vitamin C content for 24 hours, as well as at least 7 days after preparation. Conclusion: Our preliminary results confirmed that RH has antioxidative properties, significant anti-inflammatory effects, and may be useful in managing glomerulonephritisKeywords: Rose hip, glomerulonephritis, systemic lupus erythematosus, lupus, proteinuria, blood urea nitrogen, CD4+, CD8+, CD11b+Gr-1+(neutrophil), and CD11b+CD11c+ (myeloid cells)

The Case of a Patient with Limited Systemic Sclerosis and Interstitial Lung Disease Overlapping with Systemic Lupus Erythematosus

About 20% of patients with systemic sclerosis have symptoms of another connective tissue disease (CTD). Interstitial lung disease (ILD) is one of the most common organ manifestations in systemic sclerosis (SSc) as well as viral illnesses, such as COVID-19, and can lead not only to diffuse alveolar damage, but also trigger an exacerbation of fibrosis among patients with preexisting ILD. It is also associated with substantial morbidity and mortality. According to the World Scleroderma Foundation, SSc-ILD can mask or mimic early COVID-19 lesions and there are no available computed tomography guidelines on how to discern those two conditions. We present a case of systemic sclerosis exacerbation after COVID-19 in a patient with SSc-Lupus Overlap Syndrome.

Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

Eleven Myths on Nail Melanoma

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease with hamartomatous growths in multiple organs due to loss-of-function variants in TSC1 or TSC2. In approximately 15% of patients with clinical TSC, no pathogenic variant can be identified, and low-level mosaicism is suggested to be one of the reasons. Mosaicism is well-known in TSC and challenges the molecular genetic diagnosis. The advent of next-generation sequencing has improved the diagnostics in TSC including in patients with mosaicism. The TSC phenotype varies widely, and mosaic patients with TSC are often considered to have a milder phenotype. Here, the authors describe a patient with mosaic TSC with a 10% variant allele fraction and manifestations in three organ systems (skin, eyes, and kidneys). Furthermore, the authors studied existing literature about phenotypic organ manifestations in patients with mosaic TSC. No clear definition of the phenotype of patients with mosaic TSC could be established, but unilateral angiofibromas and the absence of tubers and a subependymal nodule could indicate mosaicism. The case shows that patients with low-level mosaic TSC can have multiple affected organ systems though still a mild clinical picture.

One year of COVID-19 pandemic: what we Radiologists have learned about imaging

Background Since its outbreak in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected more than 151 million people worldwide. More than 3.1 million have died from Coronavirus Disease 2019 (COVID-19), the illness caused by SARS-CoV-2. The virus affects mainly the upper respiratory tract and the lungs causing pneumonias of varying severity. Moreover, via direct and indirect pathogenetic mechanisms, SARS-CoV-2 may lead to a variety of extrapulmonary as well as vascular manifestations. Methods Based on a systematic literature search via PubMed, original research articles, meta-analyses, reviews, and case reports representing the current scientific knowledge regarding diagnostic imaging of COVID-19 were selected. Focusing on the imaging appearance of pulmonary and extrapulmonary manifestations as well as indications for imaging, these data were summarized in the present review article and correlated with basic pathophysiologic mechanisms. Results and Conclusion Typical signs of COVID-19 pneumonia are multifocal, mostly bilateral, rounded, polycyclic or geographic ground-glass opacities and/or consolidations with mainly peripheral distribution. In severe cases, peribronchovascular lung zones are affected as well. Other typical signs are the “crazy paving” pattern and the halo and reversed halo (the latter two being less common). Venous thromboembolism (and pulmonary embolism in particular) is the most frequent vascular complication of COVID-19. However, arterial thromboembolic events like ischemic strokes, myocardial infarctions, and systemic arterial emboli also occur at higher rates. The most frequent extrapulmonary organ manifestations of COVID-19 affect the central nervous system, the heart, the hepatobiliary system, and the gastrointestinal tract. Usually, they can be visualized in imaging studies as well. The most important imaging modality for COVID-19 is chest CT. Its main purpose is not to make the primary diagnosis, but to differentiate COVID-19 from other (pulmonary) pathologies, to estimate disease severity, and to detect concomitant diseases and complications. Key Points: Citation Format

Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies

Background X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation. For XLMTM several therapeutic strategies are under investigation including a study of intravenous MTM1 gene transfer using a recombinant AAV8 vector of which has some concerns arises due to hepatotoxicity. Results We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series. Conclusions We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program.

Lung fibrosis in autoimmune diseases and hypersensitivity: how to separate these from idiopathic pulmonary fibrosis

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered.

Heart valve disease in hypocomplementemic urticarial vasculitis syndrome. From immune mediated degeneration to embolic complications of infective endocarditis. A case report

Introduction Hypocomplementemic Urticarial Vasculitis Syndrome is a rare disease due to small vessel inflammation and characterized by chronic urticarial vasculitis and arthritis. Multi-organ manifestations may include glomerulonephritis, ocular inflammation (uveitis, episcleritis), and recurrent abdominal pain. To our knowledge, just other nine cases of HUVS with cardiac valvular involvement have been reported in the literature. Case summary A 32-year-old woman presented to the emergency department because of a cerebral Haemorrhage. She suffered from a severe HUVS form with cardiac valvular involvement. In the previous years, she underwent cardiac surgery twice for aortic and mitral valves immune-mediated degeneration. The neurologic event was secondary to Listeria monocytogenes aortic endocarditis, complicated by a cerebral embolism and periaortic abscess. Discussion Patients with HUVS rarely present valvular heart disease. The latter is mostly secondary to an inflammatory process. Valve degeneration and immunosuppressive therapy increase the risk of infective endocarditis, with dramatic consequences for the prognosis of these patients. Valvular involvement is a sporadic but potentially fatal complication of HUVS, which should be taken in mind in the multidisciplinary evaluation of these patients.