Manifestations Of Systemic Autoimmune Diseases Research Articles

S2044 A Rare Case of Lymphocytic Esophagitis in a Patient With Recurrent and Severe Oral Ulcers

Introduction: We describe a unique case of lymphocytic esophagitis with non-necrotizing granulomas in a patient with a three-year history of recurrent oral ulcers that did not resolve with standard medical therapy. Case Description/Methods: A 37-year-old female with a history of iron deficiency anemia presents with recurring intermittent episodes of severe oral ulcers that began after a 6-month course of antibiotics for hiradenitis suppurativa. She reported weight loss due to odynophagia and oral pain. An oral ulcer biopsy revealed dense lymphocytic and plasmocytic infiltrate with collections of histiocytic granulomas and multinucleated giant cells. Ulcer outbreaks coincided with stress and menstruation, but a gynecological etiology was unremarkable. Colonoscopy locally was non diagnostic for Crohn’s disease (CD). An obvious rheumatological etiology was not found. The patient was placed on fexofenadine once daily and a second biopsy of the oral ulcers revealed connective tissue focally surfaced by fragments of squamous epithelium, erosive lichen planus and a robust influx of mixed chronic inflammation including non-necrotizing granulomas. Further rheumatologic and dermatologic evaluation suggested an oral manifestation of Behcet’s disease. Given persistent odynophagia, esophagogastroduodenoscopy was performed. Small non-bleeding erosions in the lower third of the esophagus was found on endoscopy. Biopsies were significant for lymphocytic esophagitis with non-necrotizing granulomas and mycobacteria and fungus stains were negative. Differential diagnosis by pathology included sarcoidosis, Behcet’s disease and inflammatory bowel disease. Acid-fast and fungal stains were negative. Repeat colonoscopy including ileoscopy was negative. Management considerations by rheumatology included genetic testing for HLA-B51, steroids and colchicine. Discussion: Granulomatous esophagitis is a rare manifestation of systemic autoimmune disease including Behcet’s, Crohn’s Disease and sarcoidosis. Although only seen in 5% of CD cases, esophageal manifestations can present as granulomatous esophagitis. Pyogenic granulomatous esophagitis is typically managed with systemic corticosteroids or endoscopic resection. In our case, evaluation for Crohn’s disease was unremarkable and the presence of pathergy and involvement of non-keratinized squamous mucosa is suggestive of an oral manifestation of Behcet’s disease despite absent genital ulcers and join pain.

Ревматологические маски онкопатологии (клинический случай)

Difficulties in diagnosing system lupus erythematosus аssociated with a diverse clinical picture where new signs of the disease appear throughout the disease, and a number of symptoms disappear. There are often cases of unusual onset of the disease with absence of skin manifestations asymptomatic course of the disease. Case summary. This article presents the history of a 37-year-old patient who had manifestations of systemic autoimmune disease with autoantibodies positivity in her debut, which led to an erroneous diagnosis and inadequate treatment. Discussion. The practice of a rheumatologist increasingly notes clinical cases requiring differential diagnosis between rheumatic diseases and paraneoplastic syndrome. "Rheumatological masks" can develop in malignant tumors of different localization at different stages of the disease, showing signs of damage to the bone-joint and ligament apparatus, muscles, vessels and internal organs. Keywords: systemic lupus erythematosus, lupus-like syndrome, paraneoplastic syndrome, differential diagnostics.

Rheumatologic Disorders and the Nervous System

This article describes the neurologic manifestations of systemic autoimmune diseases. Systemic autoimmune diseases can be associated with a wide spectrum of neurologic comorbidities involving the central and peripheral nervous systems. Systemic lupus erythematosus (SLE) can be associated with a number of manifestations predominantly affecting the central nervous system (CNS), whereas peripheral neuropathy is less common. Sjögren syndrome can be associated with peripheral neuropathy in 10% of cases and CNS disease in 2% to 5% of cases. The risk of stroke is increased in SLE, rheumatoid arthritis, temporal arteritis, psoriatic arthritis, and ankylosing spondylitis. Systemic vasculitides present most commonly with mononeuritis multiplex but can also affect the CNS. Cognitive dysfunction is a common symptom among patients with systemic autoimmune diseases, most commonly seen in patients with SLE or Sjögren syndrome. Neurologic manifestations of systemic autoimmune disease are important to recognize, as they may often be the presenting manifestation leading to diagnosis of the systemic disease or may be associated with increased morbidity, other complications, or mortality. Timely diagnosis and institution of appropriate treatment, often requiring multidisciplinary care, is essential to minimize morbidity and decrease the risk of permanent neurologic deficits.

Quantification of Ocular Biomechanics In Ocular Manifestations of Systemic Autoimmune Diseases

ABSTRACTPurpose: To quantify biomechanical change associated with autoimmune diseases using Corvis ST deformation data.Methods: Cross-sectional, observational, case control study of 76 patients with systemic autoimmune disease and 21 control subjects. All patients underwent detailed ophthalmic examination with Corvis-ST (Oculus Optikgerate Gmbh, Germany) measurements for biomechanical properties of the eye.Corneal deformation and also deformation caused by the extracorneal tissue were recorded. Using a mathematical formula, the three parameters, namely, corneal stiffness (kc), extracorneal tissue stiffness (kg), and extracorneal tissue viscosity (μg), were defined.Results: The biomechanical analysis showed that kc and μg were significantly lower in patients with systemic autoimmune disease with eye manifestations than control group. However statistically, it was significant in rheumatoid arthritis (RA) patients only.Conclusion: The new parameters, namely, kc, kg, and μg, can provide a sensitive marker of the ocular activity of the collagen vascular diseases.

FRI0390 Therapeutic Plasma Exchange (TPE) for Refractory Autoimmune Diseases: Report of 60 Cases

BackgroundTherapeutic Plasma Exchange (TPE) is an effective therapeutic option for treating serious manifestations of systemic autoimmune diseases. More data about real life experience regarding outcomes of those patients are required.ObjectivesThis...

Afectación pericárdica en enfermedades de patogenia inmunológica, infecciosa y endocrinológicas

The pathology of pericardium has multiple etiologies, and can occur as a manifestation of systemic diseases. Systemic disorders that cause pericardial disease are: autoimmune diseases, neoplastic diseases, and metabolic diseases. Metabolic diseases are divided in two groups: diseases secondary to renal failure and endocrine diseases. Pericardial disease is common in patients with renal failure, even in patients on dialysis. Myxedema is an endocrine disorder frequently associated with pericardial disease. Pericardial disease represents one of the most important clinical manifestations of systemic autoimmune disease and it is an important factor in the diagnosis of immune disorders. Finally, neoplastic pericarditis is frequently caused by lung cancer and breast cancer.

Recambio plasmático en las enfermedades autoinmunes sistémicas

Therapeutic apheresis encompasses a large number of techniques whose main purpose is to process patients’ blood through an extracorporeal device. The aim is to remove antibodies and preformed immune complex to avoid tissue damage, eliminate inflammatory mediators – such as complement and cytokines, which could contribute to further damage – restore deficiencies, and stimulate lymphocyte clones to improve the response to immunosuppressive therapy.Among the different types of apheresis, the most commonly used for the treatment of autoimmune diseases are plasma exchange and immunoadsorption.To aid the correct use of these procedures, the American Society for Apheresis has established more than 65 indications classified into different categories according to the level of evidence. In this review, we analyze the distinct therapeutic indications for the treatment of different autoimmune diseases.This review indicates that plasma exchange is a safe and effective therapeutic option for treating the serious manifestations of systemic autoimmune diseases and is a valid option for those patients with diseases refractory to conventional treatments.

Relationship between Fetuin-A and Systemic Lupus Erythematosus as a Predictor Marker for Atherosclerosis

Problem statement: Associations between serum levels of fetuin-A, C3 complement, calcium × phosphate product and calcification risk index and lipid profile in SLE patients were established. However, the mechanism of accelerated atherosclerosis accompanied with SLE remains elusive. We therefore turned to investigate the association between Fetuin-A, disease activity and accelerated atherosclerosis in patients with SLE. Approach: Serum blood samples were taken from 100 female SLE patients. All Patient samples were analyzed by ELISA for determination of Fetuin-A level. Calcium, Phosphate, C3 compelement, Lipid profile, Creatinine and urea were measured also in SLE patients compared with healthy control volunteers. Results: We found that Serum fetuin-A had been positively associated with carotid arterial stiffness, independent of known atherogenic factors in healthy subjects. Furthermore, Fetuin-A was correlated negatively with IMT, SLEDAI, CRI, CaxP product, Triglycerdies, VLDL and LDL. While it was correlated positively with C3 complement. Conclusion: Fetuin-A deficiency accompanied with increasing levels of calcium and phosphate gave an evidence that there was a key role of fetuin-A as a strong inhibitor of Cardio Vascular Calcification (CVC) by formation of a complex called (calciprotein) with calcium and phosphate in blood stream. So, Identification of biologic markers of disease activity associated with atherosclerosis may help to optimize therapy for this important manifestation of systemic autoimmune disease.

Investigation and Treatment of a Complicated Inflammatory Aortoiliac Aneurysm

Inflammatory abdominal aortic aneurysms (IAAAs) account for 5% to 10% of all abdominal aortic aneurysms, occurring primarily in males. Their true etiology is unknown. Symptoms and signs of IAAA are so variable that they present to a wide range of specialties. There is debate in the literature whether IAAA is a manifestation of systemic autoimmune disease. We describe the case of a young female patient with complicated inflammatory aortoiliac aneurysmal disease, illustrating diagnostic and treatment challenges that remain. Our patient had a positive autoantibody screen, raised erythrocyte sedimentation rate, positive enzyme-linked immunosorbent spot test, and saccular aneurysms, including infective and inflammatory etiologies in her differential diagnosis. Early diagnosis is crucial to limit disease progression, morbidity, and mortality. Medical management is important to address the underlying disease process, but a combination of endovascular and open surgical intervention is often necessary for definitive treatment. Available evidence offers plausibility for benefit of endovascular intervention over open repair.

The emerging link between autoimmune disorders and neuropsychiatric disease.

Abnormal autoimmune activity has been implicated in a number of neuropsychiatric disorders. In this review, the authors discuss a newly recognized class of synaptic autoimmune encephalitides as well as behavioral and cognitive manifestations of systemic autoimmune diseases.

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

Abnormal autoimmune activity has been implicated in a number of neuropsychiatric disorders. In this review, the authors discuss a newly recognized class of synaptic autoimmune encephalitides as well as behavioral and cognitive manifestations of systemic autoimmune diseases.

Skeletal manifestations of systemic autoimmune diseases

There is an increased risk of osteoporotic fractures and osteonecrosis often at a young age among patients with certain systemic autoimmune diseases. The loss of bone mineral density and bone integrity seen with these diseases often cannot be explained by traditional risk factors alone. In this review, we focus on rheumatoid arthritis and systemic lupus erythematosus, two systemic autoimmune diseases in which skeletal manifestations have been well described. There is recent evidence that autoimmunity and its associated inflammation and vitamin D deficiency play key roles in the pathogenesis of adverse skeletal effects. Understanding these processes carries implications for the prevention and treatment of osteoporosis and osteonecrosis among patients with autoimmune diseases.

Gαq-containing G proteins regulate B cell selection and survival and are required to prevent B cell–dependent autoimmunity

Survival of mature B cells is regulated by B cell receptor and BAFFR-dependent signals. We show that B cells from mice lacking the Gαq subunit of trimeric G proteins (Gnaq−/− mice) have an intrinsic survival advantage over normal B cells, even in the absence of BAFF. Gnaq−/− B cells develop normally in the bone marrow but inappropriately survive peripheral tolerance checkpoints, leading to the accumulation of transitional, marginal zone, and follicular B cells, many of which are autoreactive. Gnaq−/− chimeric mice rapidly develop arthritis as well as other manifestations of systemic autoimmune disease. Importantly, we demonstrate that the development of the autoreactive B cell compartment is the result of an intrinsic defect in Gnaq−/− B cells, resulting in the aberrant activation of the prosurvival factor Akt. Together, these data show for the first time that signaling through trimeric G proteins is critically important for maintaining control of peripheral B cell tolerance induction and repressing autoimmunity.

Copy number variation at theFCGRlocus includesFCGR3A, FCGR2CandFCGR3Bbut notFCGR2AandFCGR2B

Human Fcgamma receptors (FcgammaRs) are glycoproteins that bind the Fc region of IgG. The genes encoding the low-affinity FcgammaRs are located on chromosome 1q23-24. Beside single nucleotide polymorphisms (SNPs), gene copy number variation (CNV) is now being recognized as an important indicator for inter-individual differences. Recent studies on identifying CNV in the human genome suggest large areas at chromosome 1q23-24 to be involved, and CNV in this region has been associated with manifestations of systemic autoimmune disease. To study both SNPs and CNV of the low-affinity FcgammaRs in one assay, we have developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. A novel CNV for FCGR3A was observed. Similar to FCGR3B and FCGR2C, a gene-dosage effect of FCGR3A was found, that seemed to correlate nicely with the FcgammaRIIIa expression on NK cells. Next, we delineated the approximate boundaries of CNV at the FCGR locus. Variation in co-segregation of neighboring FCGR genes was limited to four variants, with patterns of Mendelian inheritance. No CNV of the FCGR2A and FCGR2B genes was observed in over 600 individuals. In conclusion, we report a novel CNV of the FCGR3A gene that correlates with FcgammaRIIIa expression and function on NK cells. Only FCGR3A, FCGR2C and FCGR3B show CNV, in contrast to FCGR2A and FCGR2B.

Behcet’s disease is associated with increased concentrations of antibodies against phosphatidylserine and ribosomal phosphoproteins

Although Behcet's disease (BD) is classified among the vasculitides laboratory diagnostic does not include regularly autoantibodies associated with vascular manifestations of systemic autoimmune diseases. Twelve consecutive BD patients were studied for autoantibodies associated with vascular manifestations of systemic autoimmune diseases, HLA frequencies, and possible neurological involvement using neurophysiological methods and MRI. HLA-C*15 and C*16 frequencies were significantly (p < 0.05) higher in the patients compared with a reference population. Immunoglobulin G concentrations of antiphosphatidylserine and antiribosomal phosphoprotein antibodies were significantly elevated in BD patients when compared with healthy controls. The increased frequencies of HLA-C alleles in BD patients may stress the role of NK cells in the pathogenesis of this disease. Antiphosphatidylserine autoantibodies may in view of their role in apoptosis be involved in the development of vasculitis in BD. Because concentrations of antiphosphatidylserine and antiribosomal phosphoprotein antibodies were increased in BD diagnostic tools of this disease should be extended with humoral parameters associated with vascular manifestations of systemic autoimmune diseases.

Renal manifestations of systemic autoimmune disease: diagnosis and therapy

Renal involvement is relatively common in certain systemic autoimmune diseases, but can be clinically silent. Active surveillance is, therefore, essential because the early recognition of renal involvement may influence the extent of renal recovery. Blood pressure control is also essential, regardless of the underlying disease. In systemic lupus erythematosus, therapy usually depends on the renal biopsy findings as not all forms of renal involvement respond in the same way. Typically, for aggressive disease, therapy is with steroids and a cytotoxic agent, usually cyclophosphamide initially and then azathioprine. In systemic vasculitis with renal involvement, a similar approach is adopted, therapy including steroids and cyclophosphamide initially and then steroids and azathioprine. With severe fulminant disease, plasma exchange or pulsed intravenous methylprednisolone is added initially. Scleroderma renal crises are managed by blood pressure control using angiotensin-converting enzyme inhibitors and other agents as required. Dialysis and transplantation can be successful in these conditions.

Pulmonary manifestations of systemic autoimmune disease

Patients with systemic autoimmune disease may present with a number of different pulmonary manifestations. In order to recognise, diagnose and manage these manifestations, it is necessary to have a working knowledge of the anatomy and physiology of the thorax. This chapter will describe the clinical symptoms and clinical examination findings in patients who may have underlying pulmonary disease. It will describe the investigations that can be used to confirm or refute a possible diagnosis and describe approaches to managing these complex clinical cases. The importance of multidisciplinary teamworking using the skills of clinicians, radiologists and pathologists will be highlighted. The use of high-resolution computed tomography scanning of the thorax to help to delineate the type of interstitial lung disease will be described and some of the newer modalities available for the treatment of pulmonary hypertension introduced. By the end of the chapter, the reader should understand that patients with a single underlying autoimmune disease may present with one or more pulmonary manifestations and that different autoimmune diseases may present with similar pulmonary manifestations. This heterogeneity poses both diagnostic and treatment challenges, and many questions still remain regarding optimal treatment.

Pulmonary manifestations of systemic autoimmune disease

Patients with systemic autoimmune disease may present with a number of different pulmonary manifestations. In order to recognise, diagnose and manage these manifestations, it is necessary to have a working knowledge of the anatomy and physiology of the thorax. This chapter will describe the clinical symptoms and clinical examination findings in patients who may have underlying pulmonary disease. It will describe the investigations that can be used to confirm or refute a possible diagnosis and describe approaches to managing these complex clinical cases. The importance of multidisciplinary team working using the skills of clinicians, radiologists and pathologists will be highlighted. The use of high-resolution computed tomography scanning of the thorax to help to delineate the type of interstitial lung disease will be described and some of the newer modalities available for the treatment of pulmonary hypertension introduced. By the end of the chapter, the reader should understand that patients with a single underlying autoimmune disease may present with one or more pulmonary manifestations and that different autoimmune diseases may present with similar pulmonary manifestations. This heterogeneity poses both diagnostic and treatment challenges, and many questions still remain regarding optimal treatment.

Renal manifestations of systemic autoimmune disease: diagnosis and therapy.

Renal involvement is relatively common in certain systemic autoimmune diseases, but can be clinically silent. Active surveillance is, therefore, essential because the early recognition of renal involvement may influence the extent of renal recovery. Blood pressure control is also essential, regardless of the underlying disease. In systemic lupus erythematosus, therapy usually depends on the renal biopsy findings as not all forms of renal involvement respond in the same way. Typically, for aggressive disease, therapy is with steroids and a cytotoxic agent, usually cyclophosphamide initially and then azathioprine. In systemic vasculitis with renal involvement, a similar approach is adopted, therapy including steroids and cyclophosphamide initially and then steroids and azathioprine. With severe fulminant disease, plasma exchange or pulsed intravenous methylprednisolone is added initially. Scleroderma renal crises are managed by blood pressure control using angiotensin-converting enzyme inhibitors and other agents as required. Dialysis and transplantation can be successful in these conditions.

Thoracic manifestations of systemic autoimmune diseases: radiographic and high-resolution CT findings.

The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. They can cause a variety of thoracic abnormalities that are influenced by the pathophysiologic characteristics of the underlying disease process. Although many of the abnormalities can be detected at chest radiography, high-resolution computed tomography (CT) has been shown to be superior in depicting parenchymal, airway, and pleural abnormalities. Thoracic manifestations of collagen vascular diseases include pleural disease, pulmonary fibrosis, diaphragm weakness, aspiration pneumonia, bronchiolitis obliterans organizing pneumonia, bronchiolitis obliterans, and bronchiectasis. Wegener granulomatosis may be associated with multiple nodules or masses with irregular margins that are frequently cavitated. Patients with Churg-Strauss syndrome often have consolidation or ground-glass attenuation at chest radiography and CT. Goodpasture syndrome is associated with extensive bilateral air-space consolidation.