Manifestation Of Systemic Disease Research Articles

Intestinal Dysbiosis and Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is a chronic fibro-inflammatory disorder of the pancreas. Recent clinicopathological analysis revealed that most cases of AIP are pancreatic manifestations of systemic IgG4-related disease (IgG4-RD), a newly established disease characterized by enhanced IgG4 antibody responses and the involvement of multiple organs. Although the immuno-pathogenesis of AIP and IgG4-RD has been poorly defined, we recently showed that activation of plasmacytoid dendritic cells (pDCs) with the ability to produce large amounts of IFN-α and IL-33 mediates chronic fibro-inflammatory responses in experimental and human AIP. Moreover, M2 macrophages producing a large amount of IL-33 play pathogenic roles in the development of human IgG4-RD. Interestingly, recent studies including ours provide evidence that compositional alterations of gut microbiota are associated with the development of human AIP and IgG4-RD. In addition, intestinal dysbiosis plays pathological roles in the development of chronic pancreatic inflammation as dysbiosis mediates the activation of pDCs producing IFN-α and IL-33, thereby causing experimental AIP. In this Mini Review, we focus on compositional alterations of gut microbiota in AIP and IgG4-RD to clarify the mechanisms by which intestinal dysbiosis contributes to the development of these disorders.

A service evaluation of pediatric oral mucosal disease experience in a tertiary joint pediatric-oral medicine clinic

<h3>Objectives</h3> The true global prevalence of pediatric oral mucosal disease has historically proved difficult to determine, based on heterogeneity and inherent limitations in study designs and a largely descriptive narrative. The 2019 World Workshop on Oral Medicine VII: Relative Frequency of Oral Mucosal Lesions in Children, a Scoping Review quantified pediatric oral mucosal disease experience globally based on pooled and region-specific data from clinical studies and biopsy reports. The aim of this investigation was to retrospectively review clinical data to compare pediatric disease experience in a tertiary joint pediatric-oral medicine clinic at the Royal National ENT and Eastman Dental Hospital, UCLH, London, UK, with published global data from the world workshop. <h3>Methods</h3> Quantitative analysis was retrospectively performed on recorded clinical data from 22 joint clinics attended between January and December 2018, with recording of patient demographic characteristics, diagnosis, investigations, and management. <h3>Results</h3> Two hundred sixty-six patients (143 males, 128 females; age range, 8 months to 18 years) were seen in 2018. Referring clinicians included general dental practitioners (n = 54; 49%), secondary care medical and dental specialties (n = 33; 30%), community dental services (n = 15; 14%), and general medical practitioners (n = 9; 8%). Medical comorbidities were noted in 62 patients (23%). Idiopathic recurrent aphthous stomatitis (n = 65; 24%,), mucocele (n = 24; 9%), oral Crohn disease/orofacial granulomatosis (n = 18; 7%), and geographic tongue (n = 11; 4%) were the most commonly presenting conditions. Malignancy was the primary diagnosis in only 1 patient (mucoepidermoid carcinoma). Investigations performed included imaging (n = 27; 11%), blood tests (n = 26; 10%), and biopsy procedures (n = 23; 9%). Management included the use of topical analgesics (n = 71; 27%), topical corticosteroids (n = 94; 35%), topical calcineurin inhibitors (n = 19; 7%), and systemic immunomodulation (n = 22; 8%). <h3>Conclusions</h3> Similarity to world workshop conclusions was noted, with a predominance of benign oral mucosal disease within this patient demographic. Roughly 1 in 10 patients required investigation by imaging, blood testing, or biopsy. Although the world workshop data represented mostly transient conditions with an infectious or traumatic etiology, within this cohort, there was a greater representation of the oral manifestations of systemic disease, which may well represent the tertiary nature of referral to this unit.

Oral and Maxillo-Facial Manifestations of Systemic Diseases: An Overview.

Many systemic (infective, genetic, autoimmune, neoplastic) diseases may involve the oral cavity and, more generally, the soft and hard tissues of the head and neck as primary or secondary localization. Primary onset in the oral cavity of both pediatric and adult diseases usually represents a true challenge for clinicians; their precocious detection is often difficult and requires a wide knowledge but surely results in the early diagnosis and therapy onset with an overall better prognosis and clinical outcomes. In the current paper, as for the topic of the current Special Issue, the authors present an overview on the most frequent clinical manifestations at the oral and maxillo-facial district of systemic disease.

Characteristics of dermatology clinical trials 2007-2018: Insights from a systematic analysis of ClinicalTrials.gov

Characteristics of dermatology clinical trials 2007-2018: Insights from a systematic analysis of ClinicalTrials.gov

Knowledge, Attitude and Perception of Oral Diseases Presented by the Patients to General Medicine Practitioners in the Suburban areas of Nagpur City.

General Medicine Practitioners (GPs) are often the first point of contact for advice and management in cases of dental related pain. The reasons for presentation to the General Practitioners, rather than the dentist, include non-classic presentation of dento-facial pain, lack of coordinated after hours dental care, poor patient education, patients’ prescription of their GP as the primary coordinator of integrated total health care and financial considerations. This study aims to assess the knowledge, attitude and awareness of the common oral diseases and to create awareness of the prevailing dental conditions among general practitioners, techniques for better diagnosis, and appropriate management protocols for different dental conditions.A questionnaire study was carried out among 130 General Practitioners in the suburban areas of Nagpur City using an online survey tool. 21 questions related to dental or denture-related problems and benign and malignant disease were presented in the questionnaire. The doctors have spent an average of 5 minutes to finish the survey. The data was analyzed using descriptive statistics. Out of 130 General Practitioners 71 were well versed about plaque and calculus, whereas 86% felt that referral of the patient to a dentist is the more appropriate way to treat a dental abscess. The results of the study show that general practitioners had good dental knowledge. They were well aware about most of the dental conditions, along with the various oral manifestations of systemic diseases, and life threatening conditions. It is essential that the general practitioners should keep their knowledge updated with time. Oral health education can be included in the medical curriculum to emphasize a positive attitude towards oral health.&#x0D;

A brief review on classification of oral ulcerative lesions

Oral cavity is considered as a mirror of systemic diseases. The oral cavity consists of the lips, teeth, gums, oral mucous membranes, palate, tongue and oral lymphoid system. Various diseases affect the oral cavity of which ulcers are one of the most common disease. While most diseases of the oral cavity can be diagnosed by visual inspection, some disorders can be perplexing and their diagnoses may be elusive. They can be represented as manifestation of systemic disease or can have a specific etiology behind the disease. This article highlights the causes of oral ulcers and various classification added to it. Keywords: Oral ulcers, Chemotherapy, Aphthous.

Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sjögren's syndrome.

Myd88 activation is an important driver of autoimmunity. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by exocrine gland dysfunction in combination with serious systemic disease manifestations. Myd88-dependent signaling networks remain incompletely understood in the context of pSS. The objective of this study was to establish the contribution of tissue-specific Myd88 activation to local (exocrine) and systemic pSS manifestations. To this end, we generated two novel conditional knockout pSS mouse models; one lacking Myd88 in hematopoietic cells and a second strain in which Myd88 was deleted in the stromal compartment. Spontaneous production of inflammatory mediators was altered in salivary tissue, and nephritis was diminished in both conditional knockout strains. In contrast, pulmonary inflammation was increased in mice lacking Myd88 in hematopoietic cells and was reduced when Myd88 was ablated in stromal cells. Finally, anti-nuclear autoantibodies (ANAs) were attenuated in pSS mice lacking Myd88 in immune cells. Additionally, the ANA-specific B cell repertoire was skewed in the Myd88-deficient strains. Collectively, these data demonstrate that Myd88 activation in specific cell types is essential for distinct aspects of pSS pathology.

12. Review of diabetic papillitis

Diabetic papillitis (used interchangeably with diabetic papillopathy) is a relatively rare ocular manifestation of systemic diabetic disease. Found in both type 1 and type 2 diabetic patients, it manifests as swelling of the optic nerve head in one or both eyes and is considered a diagnosis of exclusion. Signs and symptoms of optic nerve disease are not necessarily present, and there may be spontaneous recovery. The pathogenesis is poorly understood. The following discussion will cover the presentation, diagnosis, treatment, and prognosis of diabetic papillopathy.

Influence of mandibular fracture on the dynamics of cytolytic and hepatodepressive syndromes among wounded people with massive external bleeding and usage of a tourniquet

Introduction. Injuries in today's urban society are an urgent problem. In modern trauma, along with the lesion of various anatomical parts of the body increases the frequency of damages of the extremities main vessels with the development of massive external bleeding. Under these conditions, the only way to escape is to apply a tourniquet lasting up to two hours. At the same time in the structure of militant trauma and injuries in peacetime there is a tendency to increase the frequency of injuries of the maxillofacial area. The main cause of the injured people death is the development of systemic disorders with secondary lesions of tissues and organs remote from the site of direct injury. However, the role of mandible fracture in the development of systemic disorders in the case of acute blood loss and ischemia-reperfusion of the limb is insufficiently studied.Purpose: to establish peculiarities of the liver dysfunction indicators among wounded people under conditions of mandible fracture, gunshot damage of the lower extremity soft tissues with massive external bleeding.Materials and methods. Extracts from the electronic database of Medical Cards of inpatients military personnel who were treated at the National Military Medical Clinical Center "General Military Clinical Hospital" and were injured during the anti-terrorist operation / joint force operation from 2014 to 2019 were retrospectively analyzed. Among them the results of examinations and treatment of 10 wounded patients were selected, they had isolated gunshot wounds of soft tissues of the thigh with massive external blood loss and 8 wounded patients with similar gunshot wounds, and they had additional non-gunshot fractures of the mandible. All the wounded people were immediately provided with hemostatic tourniquet proximal on the injured hip.Shock index, indicators of cytolytic syndrome (activity of serum alanine and aspartate aminotransferases (ALT, AST), the content of total and conjugated serum bilirubin) and hepatodepressive syndrome (serum total protein and albumin) were taken into account from the medical records. Indicators were recorded at the time of admission to the hospital, after 6-7 days and at the time of discharge from the hospital. Additionally, the duration of patients staying in the hospital in each of the examination groups was analyzed.Research results and their discussion. At the time of admission to the hospital wounded patients of both observation groups had a significant increase of the shock index, serum activity of ALT and AST, the content of total and direct bilirubin. During treatment of the wounded patients with additional mandible fractures up to 6-7 days, serum activity of ALT, AST and direct serum bilirubin was significantly higher, and total serum protein content was lower compared to wounded patients without mandible fracture.Conclusion. Additional mandible fracture among wounded people with gunshot damage of the thigh, massive blood loss and ischemia-reperfusion of the limb significantly impairs the functional state of the liver with a maximum of 6-7 days in hospital and is an important factor in systemic manifestations of traumatic disease, which should be considered in clinical conditions.

Lupus and the Lungs: The Assessment and Management of Pulmonary Manifestations of Systemic Lupus Erythematosus.

Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout the course of their disease. This can include disorders of the lung parenchyma (such as interstitial lung disease and acute pneumonitis), pleura (resulting in pleurisy and pleural effusion), and pulmonary vasculature [including pulmonary arterial hypertension (PAH), pulmonary embolic disease, and pulmonary vasculitis], whilst shrinking lung syndrome is a rare complication of the disease. Furthermore, the risks of respiratory infection (which often mimic acute pulmonary manifestations of SLE) are increased by the immunosuppressive treatment that is routinely used in the management of lupus. Although these conditions commonly present with a combination of dyspnea, cough and chest pain, it is important to consider that some patients may be asymptomatic with the only suggestion of the respiratory disorder being found incidentally on thoracic imaging or pulmonary function tests. Treatment decisions are often based upon evidence from case reports or small cases series given the paucity of clinical trial data specifically focused on pulmonary manifestations of SLE. Many therapeutic options are often initiated based on studies in severe manifestations of SLE affecting other organ systems or from experience drawn from the use of these therapeutics in the pulmonary manifestations of other systemic autoimmune rheumatic diseases. In this review, we describe the key features of the pulmonary manifestations of SLE and approaches to investigation and management in clinical practice.

Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis.

BackgroundWild‐type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.ObjectiveTo study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.Materials and methodsA total of 250 patients, aged 50–89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0‐4. All patients with grade 3‐4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT‐proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.ResultsAmyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3‐4; all had fibril type A (mixture of full‐length TTR and fragmented TTR). Twenty‐nine of 42 patients with grade 3‐4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome.ConclusionsThe prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.

Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease.

In Crohn's disease and ulcerative colitis, inflammation is not limited to the digestive tract. Extraintestinal manifestations (EIMs), which affect up to 50% of patients, can substantially impair quality of life. EIMs may parallel luminal disease activity or have an independent course. They most commonly involve the musculoskeletal system (e.g., peripheral or axial arthritis) and skin (e.g., erythema nodosum and pyoderma gangrenosum). Less commonly, the hepatobiliary tract (e.g., primary sclerosing cholangitis [PSC]) and the eye (e.g., episcleritis, scleritis, and uveitis) are involved. Although the pathophysiology of EIMs is poorly understood, they are likely either manifestations of a primary systemic immune disease with variable expression amongst organs, or secondary phenomena to bowel inflammation. Additional pathophysiologic mechanisms may include aberrant lymphocyte homing mediated by ectopic expression of gut-specific chemokines and adhesion molecules, cross-reactivity between microbial and self-antigens, autoantibodies against epitopes shared by the intestine and extraintestinal tissues, elevated serum concentrations of cytokines, and alterations in innate immunity. Many EIMs independent of intestinal disease activity can be successfully treated with tumor necrosis factor (TNF) antagonists. The efficacy of vedolizumab-a monoclonal antibody targeting the α4β7 integrin-for the treatment of EIMs is uncertain, but data are emerging from post hoc analyses of randomized controlled trials, prospective and retrospective cohort studies, and case series. Vedolizumab may be effective in treating EIMs related to luminal disease activity (e.g., type 1 peripheral arthritis and erythema nodosum) but has not shown biochemical improvement in PSC. Its postulated role in the development of de novo EIMs is heavily confounded by the high proportion of patients previously exposed to TNF antagonists; new EIMs could result from TNF antagonist treatment cessation rather than being caused by vedolizumab. A common limitation of clinical studies is the lack of multidisciplinary involvement in the diagnosis and monitoring of EIMs, which may lead to misdiagnosis and overreporting. Future studies should rigorously measure EIMs in parallel with objective measures of luminal disease activity to provide more robust data on the relative efficacy of new drugs, especially as increasing numbers of gut-selective compounds enter clinical development.

Neurologic Manifestations of Systemic Disease: Movement Disorders

To summarize the state of the art of therapeutic approaches for movement disorders occurring in the context of systemic disorders. These secondary movement disorders, e.g., parkinsonism, tremor, chorea, dystonia, ballism, ataxia, and dyskinesia, among others, can be transitory manifestations of systemic diseases or part of syndromes that combine systemic and neurological symptoms (e.g., Wilson’s disease). These conditions are frequently treatable and in certain cases also curable. Therefore, their recognition and treatment impact the outcomes of these patients. Most current knowledge on this topic is based on cohort studies and single case reports. There are a few large studies mostly in the context of movement disorders in cerebrovascular disease and Wilson’s disease. The management of movement disorders due to systemic disease is mostly achieved by treatment of the systemic conditions together with appropriate medical and surgical treatments for each manifestation. Specific considerations must be taken into account when managing the medications commonly used for movement disorders in the context of systemic disease compared to primary degenerative processes.

Cutaneous manifestations of severe systemic disease in children

Cutaneous manifestations of severe systemic disease in children

Dissociating Delusional Disorders and Infections from Dermatologic and Neurologic Effects of Morgellons Disease

Morgellons disease (MD) is a multi-system disorder characterized by multicolor filaments extruding out of the skin along with an array of dermatologic and neuropsychiatric symptoms. It was previously termed Delusional parasitosis. However, published scientific data found the association of MD symptoms with the systemic manifestations of Lyme disease, caused by Borrelia spirochete. In a retrospective study of 122 MD patients, skin specimens were examined and 96% of them showed Borrelia spirochete in their histology sample. Hence, this association suggests that spirochete infection could be a possible cause of chronic illness in MD patients, and this rejected the physician’s perception that MD lesions might be self-inflicted. A cohort study reported tick-borne co-infections among MD patients, which could also be an etiological factor for dermopathy in MD patients. Some literature also discussed neuropsychiatric manifestations like cognitive impairment, dementia anxiety, depression, paranoia, and sensory hallucinations in Lyme disease and associated tick-borne infection. The objectives of this review are to identify the differences in the past and current perception regarding the pathogenesis of MD and determine the associations of spirochetal and tick-borne diseases with MD and psychiatric illnesses. More than 50 new research articles and case reports were reviewed and only 31 articles were shortlisted and used as references. This review has a detailed discussion on Morgellons disease and its association with Spirochete infection.

Evaluation and Management of Asymptomatic Bradyarrhythmias.

Asymptomatic bradyarrhythmias involving sinus node dysfunction and atrioventicular blocks are frequently noted in clinical practice. Its prevalence is expected to rise as devices that are developed for monitoring cardiac rhythm for longer duration become more widely available. Episodes of bradyarrhythmia that are asymptomatic are considered to have a benign course compared with those that cause symptoms and do not necessitate further treatment. However, in certain cases, they can be a harbinger of future symptoms or cardiac manifestations of systemic diseases. The evaluation and risk stratification of individuals presenting with asymptomatic bradyarrhythmias is important not only for preventing implantation of unnecessary permanent pacing devices but also for reducing significant morbidity by implementing proper treatment as required. In this article, we will review the current evidence on the pathophysiology, diagnosis, evaluation and management of patients with asymptomatic bradyarrhythmias.

Cardiac manifestations of rheumatological disease: a synopsis for the cardiologist

### Learning objectives Cardiovascular (CV) manifestations of autoimmune systemic rheumatic diseases have become increasingly recognised and have the potential to involve any part of the heart including the myocardium, the...

Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease

BackgroundNeurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood–brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease.MethodsWe undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video-oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups.ResultsWe confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant.ConclusionsThis striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

Diseases and Surgery of the Orbit

Most orbital diseases are rarely diagnosed in the clinic. Because the consequences for the eye can be severe, it is important to recognize the signs of orbital disease early in order to initiate the correct diagnostic and therapeutic steps in good time. This article presents the basics of the systematics, diagnostics and therapy of orbital diseases in preparation for the specialist examination for ENT medicine. Some orbital diseases are typical manifestations of systemic diseases (e. g. Graves' disease) or typical complications of diseases in the vicinity of the orbit (e. g. orbital complications from inflammatory or tumorous sinus diseases). The diseases of the lacrimal system and the eyelids as well as their therapy are closely related to the diseases of the orbit. Basically, it can be said that the diagnosis and therapy of orbital diseases should always be carried out on an interdisciplinary basis, whereby the involvement of the ophthalmologist is of particular importance.

Periodontal Health and Systemic Conditions.

According to the new classification proposed by the recent 2017 World Workshop on Periodontal and Peri-implant Diseases and Conditions, periodontitis, necrotizing periodontal diseases, periodontitis as a manifestation of systemic diseases, and systemic diseases or conditions affecting the periodontal supporting tissues, are considered as separate entities. Scientific evidence has demonstrated that periodontal diseases are not just simple bacterial infections but rather complex diseases of multifactorial complexity that interplay with the subgingival microbes, the host immune, and inflammatory responses. Despite dental plaque biofilm being considered the primary risk factor for periodontitis in the vast majority of patients that dentists encounter on a daily basis, there are other factors that can also contribute and/or accelerate pathologic progressive attachment loss. In this article, the authors aim to briefly review and discuss the present evidence regarding the association between periodontal diseases and systemic diseases and conditions.