Synovial monocytes from psoriatic and rheumatoid arthritis patients are modulated differently by TNF inhibitors and glucocorticoids: an ex-vivo study.

OBJECTIVES: Synovial monocytes (expressing CD14+CD16+) affect pro-inflammatory responses in the synovium microenvironment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). The effect of various drugs on those cells was evaluated. METHODS: Synovial fluid mononuclear cells (SFMCs) from PsA (n=29) and RA (n=11) patients were cultured with biologics or glucocorticoids (GCs). CD14+CD16+ cells were analysed by flow cytometry. TNF secretion was assessed by ELISA and changes in cytokine and matrix metalloproteinase-9 (MMP-9) mRNA by qPCR. RESULTS: TNF inhibitors (i) [adalimumab (ADA) and infliximab (IFX)] significantly reduced the %CD14+CD16+ cells (p<0.04 and p<0.02, respectively) compared to IL-17Ai, IL-12/23i, and GCs in PsA patients' SFMCs. Similarly, those TNFi reduced the %CD14+CD16+ cells (p<0.05 and p<0.02, respectively) compared to IL-6Ri, CD20i and GCs in RA patients' SFMCs. TNFi (ADA p<0.01, IFX p=0.0003), and GCs (p<0.05) reduced TNF levels in PsA patients SFMCs supernatants. IFX down-regulated IL-1ß mRNA (p<0.005) while GCs betamethasone (BET) (p<0.01) and methylprednisolone acetate (MPA) (p<0.005) led to IL-1ß up-regulation. IFX down-regulated IL-8 and MMP-9 (p<0.01) and up-regulated IL-10 (p<0.005), and GCs did so to a greater extent (for IL-8, BET p<0.0001 and MPA p<0.005, for MMP-9, BET and MPA p<0.0001 and for IL-10, BET and MPA p<0.0001). CONCLUSIONS: TNFi but not GCs reduced the inflammatory monocytes. Both TNFi and GCs inhibited TNF secretion but differently modulated IL-1ß, IL-8, MMP-9 and IL-10 gene expression. Our data point to TNFi as a modulator of synovial monocytes.

Thyroid Disorders in Patients with Systemic Sclerosis: Biochemical and Sonographic Characteristics. A Prospective Cohort Study.

BACKGROUND: Patients with systemic sclerosis (SSc) are at increased risk for autoimmune thyroid diseases, but information regarding thyroid nodules and cancer in SSc is scarce. Objectives: To evaluate the thyroid gland in patients with SSc at a single Israeli center. METHODS: Thyroid workup was conducted in consecutive SSc patients: thyroid-stimulating hormone (TSH), free thyroxine (fT4), anti-thyroid peroxidase, and anti-thyroglobulin antibodies, as well as thyroid ultrasound and fine needle aspiration (FNA) when appropriate. RESULTS: Fifty patients, mean age 51.3 ± 13.5 years (44 women) were evaluated. Ten were previously diagnosed with thyroid disease. Median TSH level was 2.0 (normal range 0.23-4 mIU/l) and median fT4 level was 1.0 (normal range 0.8-2.0 ng/dL). Among the 40 thyroid disorder-naive patients, 3 had subclinical hypothyroidism and 5 had positive anti-thyroid antibodies; 22 (44%) had 1-6 thyroid nodules, which were ≥ 1 cm in 12 (24%). Accordingly, six patients underwent FNA, and five were diagnosed as colloid nodules and one as papillary carcinoma. CONCLUSIONS: New cases of clinically significant autoimmune thyroid disease were not detected in our cohort of patients with SSc. Nevertheless, almost half had thyroid nodules. The clinical significance of these findings and their relation to thyroid cancer remains to be determined.

Anti-Ro/SS-A antibody is associated with worse pulmonary outcome and reduced overall survival in systemic sclerosis.

OBJECTIVE: We sought to determine the association of anti-Ro/SS-A antibody with organ involvement and disease outcome in patients with systemic sclerosis (SSc). METHODS: A retrospective, long-term study of a cohort of incident patients diagnosed with SSc and continuously followed at our rheumatology clinic during 1990-2018. RESULTS: Included were 105 patients with known anti-Ro/SS-A antibody status, 92.4% female, mean age at diagnosis 52.0 ± 15.6 years, and median follow-up of 10 years; 64% were diagnosed with limited cutaneous SSc, 18% with diffuse cutaneous SSc, and 18% had SSc siné scleroderma or undetermined disease type. Anti-Ro/SS-A antibody tested positive in 21% of patients. In univariate analysis, anti-Ro/SS-A antibody positivity was significantly associated with SSc overlap with Sjögren's syndrome (p < .001). Predicted forced vital capacity deterioration at last encounter was significantly associated with anti-Ro/SS-A antibody positivity. In multivariate regression for anti-Ro/SS-A antibody-positive SSc patients and disease outcome [adjusted for age > 50 years, smoking, and baseline predicted forced vital capacity (pFVC) < 80%], positive anti-Ro/SS-A antibody was significantly associated with a higher all-cause mortality rate (HR 5.17, CI 95%, 1.18-22.67, p = .029), and greater deterioration of pFVC defined as a decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95%, 1.07-12.38, p = .038). CONCLUSIONS: Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc.

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study.

INTRODUCTION: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. METHODS: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose. RESULTS: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients. CONCLUSION: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

Resolution of Cannabinoid Hyperemesis Syndrome with Benzodiazepines: A Case Series.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is under-recognized by clinicians. It is characterized by nausea, severe abdominal pain, and cyclical vomiting in the context of chronic cannabis use. Oral benzodiazepine is a proposed treatment for CHS. It decreases activation of Cannabinoid Type 1 Receptor (CB1) in the frontal cortex, has a sedative and hypnotic effect and reduces the anticipation of nausea and vomiting. These effects on the central nervous system (CNS) might explain its beneficial antiemetic effect for this syndrome. OBJECTIVES: To increase the index of suspicion for CHS, a unique syndrome that requires a unique treatment with benzodiazepines and not antiemetics. METHODS: We describe a series of four patients with documented cannabis use, who were admitted to an internal medicine department of Meir Medical Center due to symptoms consistent with abdominal pain, nausea, and vomiting. They were initially treated with conventional antiemetics and proton pump inhibitors without response. Intensive investigations were conducted to exclude common and sometimes urgent gastrointestinal or CNS syndromes. RESULTS: After excluding urgent gastrointestinal and CNS origins for the vomiting, we suspected CHS. All four patients experienced similar symptoms and failure of conventional treatment with antiemetics and proton pump inhibitors. They experienced relief after administration of benzodiazepines. CONCLUSIONS: A high index of suspicion for CHS allows for rapid, appropriate treatment with benzodiazepines, which in turn may lead to cessation of the debilitating symptoms caused by this syndrome.

Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case-control study.

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (<34 weeks of gestation: 8.9% versus 0%, P < 0.01; <37 weeks of gestation: 20.5% versus 5.1%, P < 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.

Low dose naloxone for pruritus in systemic sclerosis: Case series and literature review.

RATIONALE: Pruritus is a common symptom in patients with systemic sclerosis and has a tremendous effect on the quality of life. Nevertheless, current therapeutic options are limited. The pathogenesis of pruritus in systemic sclerosis is not completely understood; however, opiate-mediated neurotransmission has been postulated to be involved. PATIENT CONCERNS AND DIAGNOSIS: We describe 4 female patients with systemic sclerosis suffering from severe pruritus, with an average 5D-itch score of 22.75. INTERVENTION AND OUTCOMES: Low-dose oral naloxone was initiated, followed by a significant improvement in the level of pruritus, reaching an average 5D-itch score of 7.5, after 6 and 12 months of treatment. None of the patients experienced side effects. LESSONS: Low-dose naloxone plays an important role in the management of pruritus in systemic sclerosis.

Lupus acute cardiomyopathy is highly responsive to intravenous immunoglobulin treatment: Case series and literature review.

INTRODUCTION: Intravenous immunoglobulin (IVIg) is currently used with considerable success for the treatment of many autoimmune diseases, including systemic lupus erythematosus (SLE). Among its various indications, IVIg has also been found to be beneficial in myocarditis, whether or not it is associated with an autoimmune disease. Nevertheless, data regarding IVIg treatment for myocarditis/cardiomyopathy in patients with SLE are sparse. The objective of this case series was to describe our experience with IVIg as a treatment for lupus myocarditis and to review the literature for IVIg for this indication. PATIENT CONCERNS: We report 5 female patients with SLE, who presented with signs of acute heart failure including pulmonary congestion and arrhythmias. DIAGNOSIS: Echocardiography demonstrated new reduced left ventricular ejection fraction of 20% to 30%. Two patients underwent coronary artery angiography, which demonstrated normal coronary arteries, supporting the diagnosis of myocarditis or nonischemic cardiomyopathy. INTERVENTIONS: High-dose IVIg treatment was initiated in all 5 patients. OUTCOMES: Following the treatment, clinical and echocardiographic improvement in cardiac function occurred within a few days to 1 month. This dramatic improvement persisted for several years. CONCLUSION: Based on our case series, we believe that IVIg has an important role in the management of lupus acute cardiomyopathy. This safe, well-tolerated optional treatment should be considered, especially in severe cases.

Systemic sclerosis induced by CNS stimulants for ADHD: A case series and review of the literature.

INTRODUCTION: Methylphenidate (Ritalin) is a CNS stimulant, and is a common treatment for children and adults with ADHD. It has been associated with Raynaud's phenomenon (RP) but not with Systemic Sclerosis (SSc). We report a case series of patients pointing out the connection between Methylphenidate and SSc. CASES: We identified three patients in a single Rheumatology clinic in Israel, who developed SSc following treatment with CNS stimulants for ADHD. All three cases had Raynaud's phenomenon, skin changes, pathological capillaroscopy and positive ANA. Symptoms appeared and worsened over months following the use of methylphenidate and subsided after its cessation. CONCLUSION: This is the first report in the literature of a causative relation between methylphenidate and the development of SSc, a serious, life-threatening condition. Patients treated with CNS stimulants should be followed closely for side-effects such as RP and skin changes.

Pregnancy outcome in severe OHSS patients following ascitic/plerural fluid drainage.

BACKGROUND: Various inflammatory cytokines have been implicated in the pathophysiology of severe ovarian hyperstimulation syndrome, as well as, various pregnancy complications, including preterm labor, pregnancy induced hypertension/preeclampsia and intra-uterine growth restriction. We aim to determine whether severe OHSS, complicated by third space fluid accumulation necessitating drainage, is associated with increased risk of late obstetrics complications. METHODS: We assessed the obstetrics and neonatal outcome measures of 16 patients admitted to our gynecology ward during a 6-year period, with severe OHSS complicated by third space fluid accumulation necessitating drainage. RESULTS: Patients delivered at 37.3 ± 5.9weeks, with a mean birth weight of 3062 ± 757 gr. There was no single case of gestational diabetes, hypertensive diseases of pregnancy, nor placental abruption. Two (12.5%) patients had preterm delivery: one at 23 weeks' gestation and one at 28 weeks' gestation following preterm premature rupture of membrane. Another patient experienced an unexplained antepartum fetal death at 27 weeks' gestation. CONCLUSIONS: Severe OHSS, complicated by third space fluid sequestration necessitating drainage, is not associated with adverse late pregnancy outcome, except probably for preterm labor. Following resolution of the OHSS, pregnancies should be regarded as any pregnancy resulting from IVF treatment, with special attention to prevent preterm labor.