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עמוד בית
Sun, 16.06.24

July 2017

Nicola Luigi Bragazzi MD PhD, Abdulla Watad MD, Mohammad Adawi MD, Howard Amital MD MHA, Gali Aljadeff BSc and Yehuda Shoenfeld MD FRCP MaACR
Original Articles
Paola Conigliaro MD PhD, Paola Triggianese MD PhD, Emiliano Giampà MD, Maria Sole Chimenti MD PhD, Barbara Kroegler MD and Roberto Perricone MD

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 


Amir Dagan, Naim Mahroum, Gad Segal, Shmuel Tiosano, Abdulla Watad, Doron Comaneshter, Arnon D. Cohen and Howard Amital

Background: Patients with giant cell arteritis (GCA) suffer from inflammatory diseases often treated by large amounts of corticosteroids. Whether this inflammatory burden also carries an increased risk for cardiovascular morbidity, and especially ischemic heart disease, is not clearly established.

Objectives: To clarify the linkage between GCA and ischemic heart disease. 

Methods: In a cross-sectional study, we assessed the association between GCA and ischemic heart disease, adjusting for cardiovascular risk factors, among GCA patients and matched controls using the database of the largest healthcare provider in Israel.

Results: The study group was comprised of 5659 GCA patients and 28,261 age and gender matched controls. The proportion of ischemic heart disease was higher in the GCA group (27.5% vs. 12.5% among controls, odds ratio 2.65). Diabetes mellitus, hypertension, hyperlipidemia and smoking were also found to have higher concurrency in GCA. After stratifying for those cardiovascular co-morbidities using logistic regression, GCA remained independently associated with ischemic heart disease with an odds ratio of 1.247 (1.146–1.357 P < 0.001).

Conclusions: GCA is associated with both cardiovascular risk factors and ischemic heart disease. Healthcare professionals should not overlook this aspect of the disease when managing GCA patients. 


Claudia Fabiani MD PhD, Giacomo Emmi MD PhD, Giuseppe Lopalco MD, Lorenzo Vannozzi MD PhD, Daniela Bacherini MD, Silvana Guerriero MD PhD, Rossella Franceschini MD, Bruno Frediani MD, Florenzo Iannone MD PhD, Gian Marco Tosi MD, Donato Rigante MD and Luca Cantarini MD

Background: The evidence on the use of dexamethasone implants in the treatment of Behçet’s disease (BD)-related uveitis is limited to a few cases. 

Objectives: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. 

Methods: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits.

Results: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. 

Conclusions: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.


Veronica Pedini MD, Isabella Savore MD and Giovanna Maria Danieli MD PhD

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immune deficiency of adulthood. Besides recurrent infections, autoimmune disorders–mainly cytopenias–affect 30% of patients with CVID.

Objectives: To describe the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIg), which is a combination of 10% [human] SCIg with recombinant human hyaluronidase for the treatment of CVID-linked cytopenias. 

Methods: We describe four women (mean age 54 years) with CVID associated with idiopathic thrombocytopenic purpura (ITP) (n=3) and autoimmune hemolytic anemia (AIHA) (n=1). Diagnosis of CVID was made according to the European Society of Immune Deficiencies / Pan-American Group for Immune Deficiency criteria. All were treated with fSCIg (bi-monthly, 20 g).

Results: After a median follow-up of 22 months, all patients achieved a stable remission from the cytopenias, characterized by increased platelet values in ITP (mean values 93000/mmc), and resolution of anemia. A reduction of the daily prednisone dose was documented in the patient with AIHA. No systemic adverse drug reactions were observed. 

Conclusions: Our preliminary data documented the efficacy and safety of fSCIg in the treatment of CVID associated with autoimmune cytopenias, with a good tolerability. We also noted the role of fSCIg as a steroid sparing agent. It is thus possible to suppose an immunomodulatory role for fSCIg, but linked to different mechanisms than IVIg, due to the peculiar pharmacokinetic and administration route of fSCIg. 


Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD MPH, Kassem Sharif MD, Ora Shovman MD, Boris Gilburd MD, Howard Amital MD and Yehuda Shoenfeld MD FRCP MACR

Background: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture’s disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture’s disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis.

Objectives: To assess the predictive value of positive anti-GBM antibodies in a clinical setting. 

Methods: Data from anti-GBM antibody tests performed at one medical center between 2006 and 2016 were systematically and retrospectively retrieved. We recruited 1914 patients for the study. Continuous variables were computed as mean ± standard deviation, while categorical variables were recorded as percentages where appropriate. Sensitivity and specificity of anti-GBM titers were calculated. Kaplan–Meyer analysis was performed, stratifying survival according to the anti-GBM antibody titers.

Results: Of the 1914 anti-GBM test results detected, 42 were positive, 23 were borderline, 142 were excluded, and 1707 results were negative. Male-to-female ratio was 1:1.2. Sensitivity of anti-GBM test was 41.2% while specificity was 85.4%. Concerning the Kaplan–Meyer analysis, overall survival was 1163.36 ± 180.32 days (median 1058 days). 

Conclusions: Our study highlights the lack of sensitivity of serological testing of anti-GBM titers. Comparing survival curves, the survival correlated with anti-GBM titer only in a borderline way. Because highly sensitive bioassays are not routinely used in clinics, renal biopsy is still pivotal for Goodpasture’s disease diagnosis.


Giuseppe Barilaro MD, Ignazio Francesco Masala MD, Renato Parracchini MD, Cesare Iesu MD, Giulia Caddia MD, Piercarlo Sarzi-Puttini MD and Fabiola Atzeni MD PhD

Hyperbaric oxygen therapy (HBOT) has been investigated as a primary/adjunctive treatment for a number of injuries and medical conditions including traumatic ischemia, necrotizing soft tissue injuries, non-healing ulcers and osteoradionecrosis, but the results are controversial. There is insufficient evidence to support or reject the use of HBOT to quicken healing or to treat the established non-union of fractures. However, in patients with fibromyalgia, HBOT reduces brain activity in the posterior cortex and increases it in the frontal, cingulate, medial temporal and cerebellar cortices, thus leading to beneficial changes in brain areas that are known to function abnormally. Moreover, the amelioration of pain induced by HBOT significantly decreases the consumption of analgesic medications. In addition, HBOT has anti-inflammatory and oxygenatory effects in patients with primary or secondary vasculitis. 

This review analyzes the efficacy and limitations of HBOT in orthopedic and rheumatologic patients.


Yackov Berkun MD, Reeval Segel MD and Paulina Navon-Elkan MD
Giorgia Bizzaro, Antonio Antico, Antonio Fortunato and Nicola Bizzaro

Vitamin D deficiency is becoming an increasing problem worldwide. It should not be underestimated, not only due to the well-known consequences vitamin D deficiency has on bone health, but primarily because recent studies have shown how the biologically active form of vitamin D – 1,25(OH)2D – is involved in many biological processes, including immune system modulation. Moreover, the presence of a vitamin D receptor was discovered in almost all immune cells and some of its polymorphisms were found to be associated with increased incidence of autoimmune diseases. This finding led to a proposed link between vitamin D deficiency and autoimmune diseases. Patients affected by various autoimmune diseases showed low levels of vitamin D. However, it is not always clear whether vitamin D deficiency is the cause or rather a consequence of the disease. Limitations of the studies, such as the small number of patients, heterogeneity of selected groups, environmental conditions, methods used to measure vitamin D serum concentration and other confounding factors do not lead to unequivocal results to demonstrate a direct link between low vitamin D levels and autoimmune disease. Therefore, randomized trials are needed to clarify conflicting results.

Donato Rigante MD, Stefano Gentileschi MD, Antonio Vitale MD, Giusyda Tarantino MD and Luca Cantarini MD PhD

Fevers recurring at a nearly predictable rate every 3–8 weeks are the signature symptom of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome, an acquired autoinflammatory disorder which recurs in association with at least one sign among aphthous stomatitis, pharyngitis, and/or cervical lymph node enlargement without clinical signs related to upper respiratory airways or other localized infections. The disease usually has a rather benign course, although it might relapse during adulthood after a spontaneous or treatment-induced resolution in childhood. The number of treatment choices currently available for PFAPA syndrome has grown in recent years, but data from clinical trials dedicated to this disorder are limited to small cohorts of patients or single case reports. The response of PFAPA patients to a single dose of corticosteroids is usually striking, while little data exist for treatment with cimetidine and colchicine. Preliminary interesting results have been published with regard to vitamin D supplementation in PFAPA syndrome, while inhibition of interleukin-1 might represent an intriguing treatment for PFAPA patients who have not responded to standard therapies. Tonsillectomy has been proven curative in many studies related to PFAPA syndrome, although the evidence of its efficacy is not widely shared by different specialists, including pediatricians, rheumatologists and otorhynolaryngologists.

Carlo Salvarani MD, Robert D. Brown Jr MD MPH and Gene G. Hunder MD
Margherita Zen MD, Mariele Gatto MD, Linda Nalotto MD, Maddalena Larosa MD, Luca Iaccarino MD PhD and Andrea Doria PhD
Case Communications
Abid Awisat, Gleb Slobodin, Nizar Jiries, Michael Rozenbaum, Doron Rimar, Nina Boulman, Lisa Kaly, Karina Zilber, Shira Ginsberg and Itzhak Rosner
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