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Frontiers in Immunology 2018Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of... (Review)
Review
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.
Topics: Autoantibodies; Autoimmune Diseases; Fibrosis; Humans; Neoplasms; Paraneoplastic Syndromes; RNA Polymerase III; Scleroderma, Systemic; Skin
PubMed: 30687318
DOI: 10.3389/fimmu.2018.03112 -
Anais Brasileiros de Dermatologia 2019Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms....
Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and α-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.
Topics: Autoantibodies; Erythema; Humans; Mouth Diseases; Paraneoplastic Syndromes; Pemphigus; Skin
PubMed: 31644609
DOI: 10.1590/abd1806-4841.20199165 -
Frontiers in Immunology 2022Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to...
BACKGROUND
Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China.
METHODS
An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored.
RESULTS
The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria.
CONCLUSION
The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Neoplasm; China; Female; Humans; Limbic Encephalitis; Male; Middle Aged; Paraneoplastic Syndromes, Nervous System; Phenotype; Retrospective Studies
PubMed: 35173717
DOI: 10.3389/fimmu.2022.790400 -
The National Medical Journal of India 2018
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Fasciitis; Female; Hand; Humans; Middle Aged; Palliative Care; Paraneoplastic Syndromes; Spinal Neoplasms
PubMed: 31134939
DOI: 10.4103/0970-258X.258234 -
BMC Psychiatry May 2017Patients with intracellular onconeural antibodies may present with neuro-psychiatric syndromes. We aimed to evaluate the evidence for an association between... (Review)
Review
BACKGROUND
Patients with intracellular onconeural antibodies may present with neuro-psychiatric syndromes. We aimed to evaluate the evidence for an association between well-characterized onconeural antibodies and psychiatric symptoms in patients with and without paraneoplastic central nervous system syndromes.
METHODS
Eligible studies were selected from 1980 until February 2017 according to standardized review criteria and evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We included studies describing the psychiatric symptomatology of onconeural antibody positive patients and the prevalence of onconeural antibodies in patients with psychiatric disorders.
RESULTS
Twenty-seven studies met the inclusion criteria. Six studies reported on the prevalence of well-characterized onconeural antibodies in patients with different psychiatric disorders, ranging from 0% to 4.9%. Antibody prevalence in controls was available from three studies, ranging from 0% to 2.8%. Data heterogeneity precluded a meta-analysis. Two cerebrospinal fluid studies found well-characterized onconeural antibodies in 3.5% and 0% of patients with psychotic and depressive syndromes, respectively.
CONCLUSIONS
The available evidence suggests that the prevalence of well-characterized onconeural antibodies in patients with psychiatric disorders is generally low. However, the question whether onconeural antibodies are important in select patients with a purely psychiatric phenotype needs to be addressed by appropriately designed studies in the future.
Topics: Antibodies, Neoplasm; Humans; Mental Disorders; Paraneoplastic Syndromes, Nervous System
PubMed: 28468645
DOI: 10.1186/s12888-017-1325-z -
Clinical and Translational... Aug 2020Intestinal pseudo-obstruction is characterized by impaired transit and luminal dilation in the absence of mechanical obstruction. Our study aims to describe the... (Comparative Study)
Comparative Study
INTRODUCTION
Intestinal pseudo-obstruction is characterized by impaired transit and luminal dilation in the absence of mechanical obstruction. Our study aims to describe the clinical, radiographic, and physiological findings in pseudo-obstruction associated with systemic sclerosis (SSc), amyloidosis, and paraneoplastic syndrome.
METHODS
A retrospective cohort of patients evaluated at our institution between January 1, 2008, and August 1, 2018, was assembled. Clinical, imaging, and physiological characteristics were abstracted from electronic medical records.
RESULTS
We identified 100 cases of pseudo-obstruction (55 SSc, 27 amyloidosis, and 18 paraneoplastic). Female population predominance was seen in SSc (71%) vs male population in amyloidosis (74%). Most common symptom was abdominal bloating in all 3 groups. Vomiting was more common in SSc than amyloidosis (73% vs 46%, P = 0.02). Diarrhea was more common in amyloidosis and SSc compared with paraneoplastic (81% and 67% vs 28%, P < 0.01). Weight loss (>5%) was more common in SSc compared with amyloidosis and paraneoplastic (78% vs 31% and 17%, P < 0.0001). Only small bowel dilation was seen in 79%, 40%, and 44% and only large bowel dilation in 2%, 44%, and 44% of patients in SSc, amyloidosis, and paraneoplastic, respectively. Five of 8 SSc patients had myopathic and 3 of 5 paraneoplastic had neuropathic involvement on gastroduodenal manometry.
DISCUSSION
SSc-associated pseudo-obstruction demonstrates female population predominance and presents with vomiting, diarrhea, and weight loss. Amyloidosis-associated pseudo-obstruction shows male population predominance. Small bowel is more commonly involved than large bowel on both imaging and transit studies in SSc. Myopathic involvement was more common in SSc, contrary to neuropathic in paraneoplastic syndrome.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amyloidosis; Diarrhea; Female; Gastrointestinal Transit; Humans; Intestinal Pseudo-Obstruction; Intestine, Small; Male; Manometry; Middle Aged; Paraneoplastic Syndromes; Retrospective Studies; Risk Factors; Scleroderma, Systemic; Sex Factors; Vomiting; Weight Loss; Young Adult
PubMed: 32931184
DOI: 10.14309/ctg.0000000000000206 -
Neurology(R) Neuroimmunology &... May 2020To investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the...
OBJECTIVE
To investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the proportion of confirmed positive results using alternative techniques.
METHODS
Sera (n = 5,300) of patients with suspected PNS were tested by PNS+2 blot (Ravo Diagnostika; January 2016-May 2017) or EUROLINE PNS 12 Ag (Euroimmun; July 2017-November 2018). Positive samples were further explored by in-house indirect immunofluorescence and a third in-house technique (Western blot or cell-based assay) using recombinant protein. Those found negative by these 2 techniques were considered as nonconfirmed. We analyzed the relationship between band intensity and final confirmation. Clinical data were collected for all confirmed results and nonconfirmed EUROLINE immunodots.
RESULTS
PNS+2 blot was positive in 128/1,658 (7.7%) sera and confirmed in 47/128 (36.7%). EUROLINE was positive in 186/3,626 (5.1%) and confirmed in 56/186 (30.1%). Confirmation was highly variable among the antibodies tested, from 7.2% (PNS+2 blot) and 5.8% (EUROLINE) for anti-Yo to 88.2% (PNS+2 blot) and 65.0% (EUROLINE) for anti-Hu. None of the 27 weak positive sera by EUROLINE was confirmed. Band intensity in confirmed cases was variable among the antibodies from strong positive for all anti-Yo (n = 3) and anti-Hu (n = 11) to positive (n = 19) or strong positive (n = 9) for anti-SOX1. Among patients with a nonconfirmed EUROLINE result and available clinical information, all had an alternative diagnosis, and only 6.7% had cancer.
CONCLUSIONS
Immunodots may be useful for PNS screening, but a threshold should be established for each antibody, and clinical information and confirmation by other techniques are essential.
CLASSIFICATION OF EVIDENCE
The study provides Class IV evidence that immunodot assays for onconeural antibodies accurately identify patients with paraneoplastic neurologic syndromes.
Topics: Autoantibodies; HEK293 Cells; Humans; Immunoblotting; Paraneoplastic Syndromes, Nervous System; Predictive Value of Tests; Retrospective Studies
PubMed: 32170044
DOI: 10.1212/NXI.0000000000000701 -
Actas Dermo-sifiliograficas 2017Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most... (Review)
Review
Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.
Topics: Adrenal Cortex Hormones; Aged; Aged, 80 and over; Antineoplastic Agents; Bexarotene; Dermatitis; Diagnosis, Differential; Disease Progression; Eosinophilia; Female; Humans; Insect Bites and Stings; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Mycosis Fungoides; Paraneoplastic Syndromes; Retrospective Studies; Tetrahydronaphthalenes
PubMed: 28342533
DOI: 10.1016/j.ad.2016.10.021 -
Dermatology Online Journal Dec 2017Paraneoplastic Pemphigus (PNP) is a rare and often fatal autoimmune mucocutaneous blistering disease associated with an underlying malignancy. It is thought to be caused...
Paraneoplastic Pemphigus (PNP) is a rare and often fatal autoimmune mucocutaneous blistering disease associated with an underlying malignancy. It is thought to be caused by antibodies to tumor antigenscross-reacting with epithelial antigens, specifically desmosomal and hemidesmosomal antigens. There are at least five clinical morphologic variants of PNP, with the earliest and most consistent finding beingsevere stomatitis. Diagnosis of PNP requires direct immunofluorescence of perilesional skin and indirect immunofluorescence. Treatment of PNP is difficult and largely limited to glucocorticoids, steroid-sparing immunomodulators, rituximab and intravenous immunoglobulin (IVIG). Despite therapies, prognosis is poor. We report a case of paraneoplastic pemphigus in a 34-year old male with severe stomatitis and lichenplanus-like cutaneous lesions.
Topics: Abdominal Neoplasms; Adult; Fibromatosis, Abdominal; Humans; Male; Paraneoplastic Syndromes; Pemphigus; Stomatitis
PubMed: 29447659
DOI: No ID Found -
Neuron Apr 2019RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact... (Review)
Review
RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA splicing, transport, and stability. Disruption of RNA binding proteins and widespread RNA processing defects are increasingly recognized as critical determinants of neurological diseases. Here, we describe distinct mechanisms by which the homeostasis of RNA binding proteins is compromised in neurological disorders through their reduced expression level, increased propensity to aggregate or sequestration by abnormal RNAs. These mechanisms all converge toward altered neuronal function highlighting the susceptibility of neurons to deleterious changes in RNA expression and the central role of RNA binding proteins in preserving neuronal integrity. Emerging therapeutic approaches to mitigate or reverse alterations of RNA binding proteins in neurological diseases are discussed.
Topics: Animals; Autophagy; CRISPR-Cas Systems; Genetic Therapy; Genetic Vectors; Homeostasis; Humans; Molecular Targeted Therapy; Nervous System Diseases; Oligoribonucleotides, Antisense; Paraneoplastic Syndromes, Nervous System; RNA; RNA Processing, Post-Transcriptional; RNA Splicing; RNA Stability; RNA Transport; RNA-Binding Proteins
PubMed: 30998900
DOI: 10.1016/j.neuron.2019.03.014