Rheumatoid Arthritis: Friedman J

Friedman J, Klepfish A, Miller EB, Ognenovski V, Ike RW, Schattner A. · Department of Medicine, Kaplan Medical Center, Rehovot and Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. · Semin Arthritis Rheum. · Pubmed #11965597 No free full text.

Abstract: OBJECTIVES: To report 2 patients who presented with agranulocytosis that was found to be immune-mediated and associated with occult primary Sjögren's syndrome (primary SS) and to identify and study similar cases reported in the literature. METHODS: Two patients encountered in 2 large medical centers over a period of 5 years were studied in detail. All reported cases of agranulocytosis in primary SS identified through a MEDLINE search were reviewed. RESULTS: Two patients presented with marked systemic symptoms alone or associated with recurrent infections. Agranulocytosis with either a pattern of maturation arrest or a hypercellular reactive bone marrow was found and was associated with "acute phase" markers, hypergammaglobulinemia, a small paraprotein peak, and high rheumatoid factor titers. A diagnosis of immune-mediated agranulocytosis associated with an occult primary SS was established and was successfully treated with intravenous immunoglobulins or prednisone. Both patients subsequently developed skin vasculitis. This rare association of agranulocytosis and Sjögren's syndrome was identified in 11 other cases and was the presenting manifestation of primary SS in 10 of 13 (77%) patients. CONCLUSIONS: Agranulocytosis should be recognized as a rare but well-established association of primary SS. Bone marrow neutrophil production may be affected, or neutrophils may be destroyed in the circulation, by both humoral and cellular immune-mediated mechanisms. Agranulocytosis or neutropenia should be added to the varied hematologic manifestations of primary SS and may be its presenting feature and an important clue to diagnosis.

Schattner A, Friedman J, Klepfish A. · Kaplan Medical Center, Hebrew University-Hadassah Medical School, Jerusalem, Israel. · Clin Rheumatol. · Pubmed #11954887 No free full text.

Abstract: A healthy woman presented with ecchymoses due to thrombocytopenia, with numerous bone marrow megakaryocytes, microangiopathic haemolytic anaemia, disorientation, irritability, and normal renal function. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and treated successfully by plasma exchange therapy, both on presentation and during a further three relapses. The TTP was considered idiopathic until, 4 months later, definite primary Sjogren's syndrome (1 degree SS) was diagnosed following the appearance of sicca symptoms. Only four similar cases have been cited in the literature. TTP should be added to the varied haematological manifestations that may occur in patients with 1 degree SS. The possible presentation of 1 degree SS not with classic sicca symptoms but rather with haematological abnormalities, including TTP, should be recognised.

Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, Rozenbaum M, Mader R, Adawi M, Caspi D, Tishler M, Langevitz P, Rubinow A, Friedman J, Green L, Tanay A, Ochaion A, Cohen S, Kerns WD, Cohn I, Fishman-Furman S, Farbstein M, Yehuda SB, Fishman P. · Can-Fite BioPharma Ltd, Petach Tikva, Israel. · J Rheumatol. · Pubmed #18050382 No free full text.

Abstract: OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.

Friedman J, Schattner A, Shvidel L, Berrebi A. · Kaplan Medical Center, Rehovot and Hebrew University Hadassah Medical School, Jerusalem, Israel. · Semin Arthritis Rheum. · Pubmed #16616153 No free full text.

Abstract: OBJECTIVE: Patients with T-cell (CD3+) large granular lymphocyte (LGL) leukemia have a high prevalence of autoantibodies and associated autoimmune diseases. Sjogren's syndrome may not be diagnosed unless specifically looked for. We set to determine the prevalence of Sjogren's syndrome in LGL leukemia and its cytokine profile. METHODS: Every patient with a confirmed diagnosis of LGL leukemia diagnosed at a single academic medical center over the last 15 years was evaluated for Sjogren's syndrome by questioning about sicca symptoms. In symptomatic patients, Schirmer's test, rose bengal corneal staining, salivary flow rate measurement, autoantibody screening, and minor salivary gland biopsy were performed. Supernatants obtained from T-LGL leukemic cells following phytohemagglutinin (PHA) activation were analyzed for cytokine production by enzyme-linked immunosorbent assay and patients with or without Sjogren's syndrome were compared with controls. RESULTS: Of 48 patients, 21 reported sicca symptoms and were enrolled in the study. In 8 patients Sjogren's syndrome was ruled out. Thirteen patients had clear evidence of Sjogren's syndrome according to accepted criteria (27%). None had rheumatoid arthritis, but 1 had limited scleroderma. Thus, 12/48 patients had primary Sjogren's syndrome. Other autoimmune diseases were frequently present, in particular, immune cytopenias (n=7) or thyroid autoimmunity (n=6). Supernatants of T-LGL leukemia cells incubated with PHA revealed markedly increased levels of multiple cytokines (especially soluble interleukin 2 receptor, tumor necrosis factor alpha, IL-6, IL-8) compared with healthy controls. However, this increase was common to LGL leukemia patients with or without Sjogren's syndrome. CONCLUSIONS: Sjogren's syndrome was commonly identified in the patients with T-cell LGL leukemia in this study. Upregulated cytokine production by the neoplastic cells may underlie some of the immune-mediated disorders common in these patients.

Schattner A, Friedman J, Klepfish A, Berrebi A. · Department of Medicine and. Hematology Unit, Kaplan Medical Center, Rehovot, and the Hebrew University-Hadassah Medical School, Jerusalem, Israel. · QJM. · Pubmed #11110590 links to  free full text

Abstract: A diagnostic delay of several years in primary Sjögren's syndrome is common, even in patients who present with sicca symptoms. It is much more likely in cases with prominent symptomatic extraglandular involvement. We report on three such patients who presented as Coomb's positive haemolytic anaemia, systemic symptoms with agranulocytosis and gingival bleeding due to immune thrombocytopenia, to alert clinicians to the fact that primary Sjögren's syndrome may present as clinically significant immune-mediated cytopenia in the absence of sicca symptoms. Sjögren's syndrome, a common autoimmune disorder, should be considered in the differential diagnosis of apparently 'idiopathic' cytopenias and actively sought by directed history, Schirmer test and autoantibody screening.

Schattner A, Friedman J, Bentwich Z. · No affiliation provided · Rheumatology (Oxford). · Pubmed #14681566 links to  free full text

This publication has no abstract.

Klepfish A, Friedman J, Schechter Y, Schattner A. · No affiliation provided · Rheumatology (Oxford). · Pubmed #11511772 links to  free full text

This publication has no abstract.