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עמוד בית
Sun, 14.04.24

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January 2024
Milena Tocut MD, Amir Tanay MD, Gisele Zandman-Goddard MD

Paraneoplastic syndromes are reported in 8–15% of patients diagnosed with cancer [1]. They are defined as syndromes that occur due to an underlying malignancy, which has yet to be diagnosed, or at the time of the diagnosis and less frequently following the diagnosis of a malignancy. Several mechanisms are involved including autocrine and paracrine mediators, hormones, peptides, cytotoxic lymphocytes, and cytokines [1,2].

September 2023
Ljudmila Stojanovich PhD, Natasa Stanisavljevic PhD, Aleksandra Djokovic PhD, Milomir Milanovic PHD, Jovica Saponjski PhD, Yehuda Shoenfeld MD FRCP MaACR

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

March 2023
Johnatan Nissan, Anna Blokh MD, Niv Ben-Shabat MD MPH, Harald Heidecke PhD, Gilad Halpert PhD, Yehuda Shoenfeld MD FRCP MaACR, Howard Amital MD MHA

Background: Fibromyalgia syndrome (FMS) is estimated to affect 2–4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN.

Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls.

Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique.

Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013).

Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Dana Arnheim MBBS BA, Arad Dotan BSc, Netta Shoenfeld MSW, Yehuda Shoenfeld MD FRCP MaACR

The interplay between post-traumatic stress disorder (PTSD) and autoimmunity is well known. One of the contributors leading to immune disorders is autonomic dysregulation, which is characterized by attenuated parasympathetic and elevated sympathetic systems. In this review, we described evidence regarding the relationship between stress, PTSD, autonomic dysfunction, and autoimmunity. Stress is a physiological response, which is functional for our being. The implication of dysfunction in stress response may be a cause of disease development. We described the fundamental role of the pathological high levels of stress in PTSD as a mediator factor that contributes to autonomic dysfunction, which as a result may lead to autoimmunity. Systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes are some of the autoimmune diseases PTSD patients are at higher risk of developing. Notably, some autoimmune diseases are shown to increase the susceptibility to develop PTSD, which may indicate a bidirectional influence. In addition, we elaborated on stress as a major component in both fibromyalgia and PTSD, as there are overlaps between the pathogenesis of fibromyalgia and PTSD. Underlying chronic low-grade inflammation, which characterizes PTSD patients, may be a potential target and biomarker in treating PTSD patients. We believe that chronic low-grade inflammation, high concentrations of cytokines, and other inflammatory biomarkers, which characterize PTSD patients, may be potential targets and biomarkers in the treatment of PTSD patients and part of the PTSD diagnostic criteria.

June 2022
Shir Rubinstein Levy B Med Sc, Gilad Halpert PhD, and Howard Amital MD MHA

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

January 2022
Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD, and Yehuda Shoenfeld MD FRCP MaACR
July 2019
Laura Andreoli MD PhD, Antía García-Fernández MD, Maria Chiara Gerardi MD and Angela Tincani MD

Rheumatic diseases commonly affect women of childbearing age, when women may be contemplating pregnancy or they discover an unplanned pregnancy. Therefore, specific issues about pregnancy planning and management are commonly encountered in patients during these times. Knowledge of the effect of pregnancy on disease activity is important for counseling. This review summarizes recent data on the course of different rheumatic diseases during pregnancy and the postpartum period. Rheumatoid arthritis and systemic lupus erythematosus are the most commonly investigated diseases. Data are increasing about spondyloarthritis. Sparse data are available for other rheumatic diseases. Despite the differences in these diseases and the various courses these disease take during pregnancy, a common feature is that active maternal disease in the months prior to conception increases the risk of flares during pregnancy, which in turn can lead to adverse pregnancy outcomes. Therefore, maternal and fetal health can be optimized if conception is planned when disease is inactive so that a treatment regimen can be maintained throughout pregnancy.

Lisa Gamalero MD, Gabriele Simonini MD, Giovanna Ferrara MD, Silvio Polizzi MD, Teresa Giani MD and Rolando Cimaz MD

Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.

January 2019
Alexandra Balbir-Gurman MD, Vika Shataylo BSc and Yolanda Braun-Moscovici MD

Background: The aggregation of autoimmune diseases in relatives (AID-R) of patients with systemic sclerosis (SSc) has been reported.

Objectives: To analyze the prevalence of autoimmune diseases in SSc relatives and to compare their features to those of SSc patients without AID-R (controls).

Methods: A case-control analysis compared SSc patients with AID-R to those without AID-R (25 patients) with similar disease duration.

Results: Among 322 patients, 25 (7.7%; 21 females, 41.4 ± 15.6 years of age, disease duration 11 ± 8.6 years) had AID-R (21 had a first-degree relative, 4 had a second-degree relative, and 2 had both). Fourteen patients (56%) and five controls (20%) had an additional autoimmune disease (P < 0.009). Diffuse SSc (48% vs. 24%) and arthritis (72% vs. 28%) were more frequent among the patients with AID-R than the controls (P < 0.05). No significant differences were found regarding lung, heart, vascular, and digestive system involvement. The mean number of additional autoimmune diseases was 0.84 ± 0.94 in AID-R vs. 0.24 ± 0.52 in controls (P < 0.038). The mean number of autoantibodies was 2.8 ± 1.5 and 2.2 ± 0.9 (P < 0.047). Five patients died during follow-up, four of whom had AID-R. Relatives of SSc patients had diverse autoimmune diseases; the prevalence of SSc in scleroderma relatives was 1.86% (2 in first-degree and 6 in second-degree relatives). SSc patients with AID-R had an obvious tendency to polyautoimmunity.

Conclusion: A precise family history is an important clue in prognosis and prediction of autoimmune diseases in SSc patients and their relatives.

October 2017
Chen Ben David MS, Kassem Sharif MD, Abdulla Watad MD, Nicola Luigi Bragazzi MD MPH PhD and Mohammad Adawi MD MHA
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