Immune Axonal Neuropathies Associated With Systemic Autoimmune Rheumatic Diseases

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.

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Ganglionic Acetylcholine Receptor Antibodies and Autonomic Dysfunction in Autoimmune Rheumatic Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21041332 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1332 ◽

Cited By ~ 2

Author(s):

Michie Imamura ◽

Akihiro Mukaino ◽

Koutaro Takamatsu ◽

Hiroto Tsuboi ◽

Osamu Higuchi ◽

...

Keyword(s):

Autonomic Dysfunction ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Acetylcholine Receptors ◽

Case Reports ◽

Pathophysiological Mechanism ◽

Autoimmune Rheumatic Diseases ◽

Immune Mediated ◽

Autonomic Disturbance ◽

Antibody Levels

Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren’s syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder, which causes dysautonomia that is mediated by autoantibodies against ganglionic acetylcholine receptors (gAChRs). The purpose of this review was to describe the characteristics of autonomic disturbance through previous case reports and the functional tests used in these studies and address the importance of anti-gAChR antibodies. We have established luciferase immunoprecipitation systems to detect antibodies against gAChR in the past and determined the prevalence of gAChR antibodies in various autoimmune diseases including AAG and rheumatic diseases. Autonomic dysfunction, which affects lower parasympathetic and higher sympathetic activity, is usually observed in ARD. The anti-gAChR antibodies may play a crucial role in autonomic dysfunction observed in ARD. Further studies are necessary to determine whether anti-gAChR antibody levels are correlated with the severity of autonomic dysfunction in ARD.

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B cell depletion in immune-mediated rheumatic diseases and coronavirus disease 2019 (COVID-19)

Rheumatology Science and Practice ◽

10.47360/1995-4484-2021-384-393 ◽

2021 ◽

Vol 59 (4) ◽

pp. 384-393

Author(s):

E. L. Nasonov ◽

A. S. Avdeeva

Keyword(s):

B Cell ◽

Rheumatic Diseases ◽

Bacterial Infections ◽

Human Monoclonal Antibody ◽

Chimeric Mouse ◽

Internal Organs ◽

Irreversible Damage ◽

Autoimmune Rheumatic Diseases ◽

Number Of Factors ◽

Immune Mediated

In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.

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EVALUATION OF ANTI-DFS70 ANTIBODIES PRE-ABSORPTION PROTOCOL FOR ANA-IIF HEP-2 TESTING IN THE DIAGNOSTIC APPROACH OF SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES

10.26226/morressier.56e174dbd462b8028d88ad4c ◽

2016 ◽

Author(s):

Alexandra Tsirogianni

Keyword(s):

Rheumatic Diseases ◽

Diagnostic Approach ◽

Autoimmune Rheumatic Diseases

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OP0147 RHEUMATIC? - A DIGITAL DIAGNOSTIC DECISION SUPPORT TOOL FOR INDIVIDUALS SUSPECTING RHEUMATIC DISEASES: A MULTICENTER VALIDATION STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1118 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 87.1-88

Author(s):

R. Knevel ◽

J. Knitza ◽

A. Hensvold ◽

A. Circiumaru ◽

T. Bruce ◽

...

Keyword(s):

Health Care ◽

Decision Support ◽

Rheumatic Disease ◽

Rheumatic Diseases ◽

Receiver Operating Curve ◽

Musculoskeletal Complaints ◽

Immune Mediated ◽

Diagnostic Decision ◽

Ocean Observations ◽

Receiver Operating

Background:Digital diagnostic decision support tools promise to accelerate diagnosis and increase health care efficiency in rheumatology. Rheumatic? is an online tool developed by specialists in rheumatology and general medicine together with patients and patient organizations for individuals suspecting a rheumatic disease.1,2 The tool can be used by people suspicious for rheumatic diseases resulting in individual advise on eventually seeking further health care.Objectives:We tested Rheumatic? for its ability to differentiate symptoms from immune-mediated diseases from other rheumatic and musculoskeletal complaints and disorders in patients visiting rheumatology clinics.Methods:The performance of Rheumatic? was tested using data from 175 patients from three university rheumatology centers covering two different settings:A.Risk-RA phase setting. Here, we tested whether Rheumatic? could predict the development of arthritis in 50 at risk-individuals with musculoskeletal complaints and anti-citrullinated protein antibody positivity from the KI (Karolinska Institutet)B.Early arthritis setting. Here, we tested whether Rheumatic? could predict the development of an immune-mediated rheumatic disease in i) EUMC (Erlangen) n=52 patients and ii) LUMC (Leiden) n=73 patients.In each setting, we examined the discriminative power of the total score with the Wilcoxon rank test and the area-under-the-receiver-operating-characteristic curve (AUC-ROC).Results:In setting A, the total test score clearly differentiated between individuals developing arthritis or not, median 245 versus 163, P < 0.0001, AUC-ROC = 75.3 (Figure 1). Also within patients with arthritis the Rheumatic? total score was significantly higher in patients developing an immune-mediated arthritic disease versus those who did not: median score EUMC 191 versus 107, P < 0.0001, AUC-ROC = 79.0, and LUMC 262 versus 212, P < 0.0001, AUC-ROC = 53.6.Figure 1.(Area under) the receiver operating curve for the total Rheumatic? scoreConclusion:Rheumatic? is a web-based patient-centered multilingual diagnostic tool capable of differentiating immune-mediated rheumatic conditions from other musculoskeletal problems. A following subject of research is how the tool performs in a population-wide setting.References:[1]Knitza J. et al. Mobile Health in Rheumatology: A Patient Survey Study Exploring Usage, Preferences, Barriers and eHealth Literacy. JMIR mHealth and uHealth. 2020.[2]https://rheumatic.elsa.science/en/Acknowledgements:This project has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union’s Horizon 2020 Research and Innovation program.This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357, RTCure.Disclosure of Interests:Rachel Knevel: None declared, Johannes Knitza: None declared, Aase Hensvold: None declared, Alexandra Circiumaru: None declared, Tor Bruce Employee of: Ocean Observations, Sebastian Evans Employee of: Elsa Science, Tjardo Maarseveen: None declared, Marc Maurits: None declared, Liesbeth Beaart- van de Voorde: None declared, David Simon: None declared, Arnd Kleyer: None declared, Martina Johannesson: None declared, Georg Schett: None declared, Thomas Huizinga: None declared, Sofia Svanteson Employee of: Elsa Science, Alexandra Lindfors Employee of: Ocean Observations, Lars Klareskog: None declared, Anca Catrina: None declared

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TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0043-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Manal Y. Tayel ◽

Aida Nazir ◽

Ibtessam M. Abdelhamid ◽

Myriam A. S. Helmy ◽

Nadia E. Zaki ◽

...

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lymphoproliferative Disorders ◽

Group Iii ◽

Autoimmune Rheumatic Diseases ◽

Group I ◽

Tnf Α ◽

Ifn Γ ◽

Tgf Β1 ◽

Distribution Frequency

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

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P052 Leflunomide and severe COVID-19 outcome: a cautionary observation from the COVID-19 Scottish Registry of Autoimmune Rheumatic Diseases (SCAR-19)

Rheumatology ◽

10.1093/rheumatology/keab247.049 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Maira Karabayas ◽

James Brock ◽

Gillian Fordyce ◽

Neil Basu

Keyword(s):

Rheumatic Diseases ◽

Clinical Characteristics ◽

National Registry ◽

Favourable Outcome ◽

Non Invasive ◽

Autoimmune Rheumatic Diseases ◽

Non Invasive Ventilation ◽

Pcr Diagnosis ◽

Related Symptom ◽

Disease Modifying

Abstract Background/Aims Leflunomide, a conventional disease modifying drug (csDMARD), is used in a variety of autoimmune rheumatic diseases (ARD) due to its immunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, due to its long half-life, drug washout procedures are often advised in the context of serious infections. Interestingly, Leflunomide is currently being tested as a potential therapy for COVID-19 in the general population. It is unknown whether leflunomide therapy is associated with a poor or favourable outcome among ARD patients infected with COVID-19. Methods A Scottish-wide registry was rapidly developed in March 2020. Clinical characteristics and outcomes of infected cases were collated across all Scottish health boards. Eligible patients included any adult leflunomide treated ARD patients with a confirmed (clinically or PCR) diagnosis of COVID-19. Results Of the 69 cases included in the registry, n = 4 were treated with leflunomide (75% female; mean age 61, SD 4.2). N = 2 were treated with combination baricitinib or hydroxychloroquine respectively, whilst n = 1 received recent corticosteroid therapy (intramuscular Kenalog). Comorbidities observed in this sub-cohort include diabetes mellitus n = 3, hypertension n = 2, cardiovascular disease n = 1, lung disease n = 1 and latent TB n = 1. At presentation, all patients (n = 4) experienced the established COVID-19 related symptom triad of dyspnoea, cough and fever and promptly developed acute respiratory syndrome. Diarrhoea was also recorded in n = 2 and constitutional upset n = 3. All patients suffered a serious COVID-19 disease outcome (defined as a requirement of invasive or non-invasive ventilation (n = 4) and/ or death (n = 2). P052 Table 1:Patient demographics, clinical characteristics and outcomesPatient 1Patient 2Patient 3Patient 4Age58635766SexFemaleFemaleMaleFemaleRheumatic diagnosisRheumatoid arthritisPsoriatic arthritisPsoriatic arthritisRheumatoid ArthritisComorbiditiesDiabetesHypertension Diabetes COPDNilIschaemic heart disease Hypertension Diabetes Latent TBClinical presentationDyspnoea Cough Fever Confusion Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetDyspnoea Cough Fever Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetAdditional csDMARD*NilNilNilHydroxychloroquinebDMARD**/ tsDMARD***BaricitinibNilNilNilSteroid therapyNilNilNilIM KenalogInvasive or non-invasive ventilationYesYesYesYesDeathNoNoYesYes* conventional disease modifying drug,**biologic disease modifying drug,***targeted synthetic disease modifying drug. Conclusion Preliminary data from this Scotland-wide registry has identified only a small number of leflunomide treated ARD patients infected with COVID-19. However, it is concerning that all cases experienced a serious outcome. Given the relatively infrequent prescription of this drug, combining similar national registry data is necessary to ensure this observation is not spurious. If confirmed, leflunomide washout procedures should be encouraged among such patients when they first present with COVID-19. Disclosure M. Karabayas: None. J. Brock: None. G. Fordyce: None. N. Basu: None.

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Osteonecrosis of the Femoral Head in Patients with Hypercoagulability—From Pathophysiology to Therapeutic Implications

International Journal of Molecular Sciences ◽

10.3390/ijms22136801 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6801

Author(s):

Elena Rezus ◽

Bogdan Ionel Tamba ◽

Minerva Codruta Badescu ◽

Diana Popescu ◽

Ioana Bratoiu ◽

...

Keyword(s):

Femoral Head ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medical Intervention ◽

Rapid Progression ◽

Anticoagulant Treatment ◽

Early Medical Intervention ◽

Therapeutic Implications ◽

Early Stages ◽

Hereditary Thrombophilia

Osteonecrosis of the femoral head (ONFH) is a debilitating disease with major social and economic impacts. It frequently affects relatively young adults and has a predilection for rapid progression to femoral head collapse and end-stage hip arthritis. If not diagnosed and treated properly in the early stages, ONFH has devastating consequences and leads to mandatory total hip arthroplasty. The pathophysiology of non-traumatic ONFH is very complex and not fully understood. While multiple risk factors have been associated with secondary ONFH, there are still many cases in which a clear etiology cannot be established. Recognition of the prothrombotic state as part of the etiopathogeny of primary ONFH provides an opportunity for early medical intervention, with implications for both prophylaxis and therapy aimed at slowing or stopping the progression of the disease. Hereditary thrombophilia and hypofibrinolysis are associated with thrombotic occlusion of bone vessels. Anticoagulant treatment can change the natural course of the disease and improve patients’ quality of life. The present work focused on highlighting the association between hereditary thrombophilia/hypofibrinolysis states and ONFH, emphasizing the importance of identifying this condition. We have also provided strong arguments to support the efficiency and safety of anticoagulant treatment in the early stages of the disease, encouraging etiological diagnosis and prompt therapeutic intervention. In the era of direct oral anticoagulants, new therapeutic options have become available, enabling better long-term compliance.

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