Hanan Gur

Autoimmune Aspects of Primary Pulmonary Hypertension

Although primary pulmonary hypertension (PPH) is considered to be an idiopathic condition, it has been postulated that autoimmunity may play a role in the pathogenesis of the disease. This argument has been based on frequent coexisting clinical and serological rheumatic findings. Moreover, approximately in a third of the patients with PPH, and antinuclear factor can be detected. Pulmonary hypertension may appear as a secondary complication to various autoimmune conditions. In light of these findings we examined sera derived from 40 patients diagnosed as having PPH for the presence of 18 different autoantibodies by the ELISA and immunofluorescent techniques. Of the 40 patients, 62.4% had circulating autoantibodies and 47.5% presented with multiantibody responses. Autoantibodies most commonly observed were antinuclear (42.5%), anti-ssDNA (25%) and antithyroglobulin (30%) antibodies. These results may imply that in a subgroup of patients with PPH the disease may be ascribed to an immune dysregulation or alternatively that autoantibodies accompany the disease progression as an epiphenomenon.

Rheumatic Manifestations Preceding Adult Acute Leukemia: Characteristics and Implication in Course and Prognosis

The manifestations and outcome of adult patients with acute leukemia (AL) were examined to study the characteristics of the rheumatological prodrome of AL and to find whether it is a marker of a distinct clinical and laboratory course and whether it has any prognostic implication. During a 10-year period, 8/139 (5.8%) of AL patients presented with rheumatic manifestations. The average duration of the arthritis syndrome preceding the diagnosis of AL was 3.25 months. The most common pattern of presentation was a reactive arthritis-like syndrome involving the large joints asymmetrically and associated with low back pain. Distinctive features suggesting a paraneoplastic arthritis were severe pain disproportionate to physical findings, a poor response to conventional antirheumatic treatment, and early significant osteopenia or lytic bone lesions. The epidemiological, clinical and laboratory characteristics of patients with or without rheumatic manifestations were comparable, except for fever on presentation, the presence of transient metabolic derangement following chemotherapy, and the initial average hemoglobin, hematocrit and serum uric acid values. Moreover, the initial outcome of the two groups was similar, as the early mortality rates were comparable (42.8% vs. 45% for patients with or without arthritis, respectively). In conclusion, rheumatic syndrome presentation of adult AL is uncommon, and apparently has no deleterious effects on initial prognosis. A timely diagnosis requires an increased awareness to distinctive features.

Lactic Acidosis and Fatal Myocardial Failure Due to Clozapine

Objective To describe a patient with neutropenic fever complicated by hyperglycemia, lactic acidosis, and fatal myocardial failure associated with clozapine therapy. Case Summary A 37-year-old Ashkenazic Jewish man was admitted for agranulocytosis and fever, which developed after 11 weeks of clozapine monotherapy for drug-resistant schizophrenia. Complete blood counts and a routine serum chemical analysis had been normal before the treatment was initiated, and remained within normal limits during the first 10 weeks of the treatment. On the day of admission, the patient deteriorated rapidly and developed extreme hyperglycemia, severe lactic acidosis, recurrent cardiac arrest, cardiogenic shock, and coma. He died 36 hours later despite intensive treatment. Discussion Clozapine intake induced fatal aganulocytosis, associated with hyperglycemia, lactic acidosis, and heart failure. White blood cell count monitoring was insufficient to predict these adverse effects. Conclusions Clozapine should be avoided in high-risk patients (e.g., the elderly, women, Ashkenazic Jews).

Autoantibody Profile of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease of unknown etiology. It has been suggested that genetic and immunological factors are important in its pathogenesis. The present study examined the prevalence of 23 different autoantibodies in 25 PSC sera, by ELISA, in order to better define the autoimmune profile of PSC. The results indicate that 88% of PSC patients produced at least 1 autoantibody, and 36% had reactivity to multiple autoantibodies. Moreover, 35% of the PSC patients produced anti-endothelial-cell antibodies (AECA) and 75% of the sera contained perinuclear antineutrophil cytoplasmic antibodies (pANCA), detected by indirect immunofluorescence. The prominent ANCA autoantibody was anti-cathepsin-G, demonstrated in 35% of the patients. The multiplicity of the autoantibody profile, revealed in the present study, points to the autoimmune characteristics of PSC. In addition, the association of ANCA and of AECA in PSC may suggest a pathogenic role for these antibodies in PSC.

RHEUMATOLOGIC FEATURES OF HEMATOLOGIC DISORDERS

This review focuses on the various rheumatologic manifestations of hematologic diseases and is based on the English literature published over the past year. Interrelationships between leukemia, lymphoma, POEMS syndrome, multiple myeloma, hemophilia, and rheumatic manifestations are discussed. Other less common associated conditions dealt with include the RS3PE syndrome, large granular lymphocyte syndrome, and interferon-related arthritis. Finally, therapeutic measures, such as bone marrow transplantation and the use of granulocyte colony-stimulating factor, are reviewed.

Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department.

We examined the efficacy and safety of intravenous amiodarone in 20 unselected patients with recent-onset atrial fibrillation who were admitted to a general internal medicine department during a 6-month period. The treatment protocol included a loading dose of 1200 mg intravenous amiodarone in 24 hours, after which amiodarone treatment was continued orally. Eleven of the 20 patients (55%) converted to sinus rhythm within 48 hours of intravenous amiodarone treatment and were discharged in sinus rhythm, while 9/20 (45%) patients failed to convert during hospitalisation. Six patients (30%) failed to convert to sinus rhythm even after one further month of oral treatment. There was one death and a high frequency (25%) of thrombophlebitis during hospitalisation. The in-hospital non-convertors had a significantly lower ejection fraction and initial low ventricular response rate than the convertors. In conclusion, the acute conversion rate by intravenous amiodarone was at best modest. It is suggested that intravenous amiodarone is probably more effective in patients with rapid recent-onset atrial fibrillation and good left ventricular function.

Unexplained fever in the ED: analysis of 139 patients

This study examined consecutive patients with unexplained fever (UF) presenting to the ED to define their characteristics and to compare distinctive parameters between admitted and discharged patients. During a 3-month period, all adult patients presenting to the ED with UF were prospectively followed for 1 month. Of 139 patients with UF, 58 patients (42%) were admitted to the hospital, whereas 81 patients (58%) were discharged. Whereas most of the discharged patients had self-limited febrile disease and eventually recovered, the admitted patients had more unresolved fever, serious infections, or systemic diseases and a 5% mortality rate. The admitted patients were older, had more comorbidity, higher leukocyte count, and anemia, but not a higher degree of fever. Older age, comorbidity, leukocytosis, and anemia, but not higher degree of fever, should direct the decision toward admission of a patient with UF.

The epidermotropic mycosis fungoides associated α1β1 integrin (VLA‐1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells

Several of the βa integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM) proteins are expressed by malignant T cells in cutaneous T‐cell lymphoma (CTCL). We evaluated the function of VLA‐1. a β1 integral specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+ leukemic T cells (Jurkat line). We found that Jurkat cells adhere significantly to collagens only after their activation with phorbol 12‐myristate 13‐acetate (PMA). However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells selected for expressing increased levels of VLA‐1 (with unchanged levels of VLA‐2, the second collagen integrin receptor) was significantly enhanced relative to that of “VLA‐1 low” cells. Monoclonal antibody (mAb) 1B3.1, directed against the collagen binding domain of VLA‐1, inhibited adhesion to collagen IV and to collagen I by 36.67%±5.25% and 18%±4.32%, respectively (p<0.05), whereas the inhibition by anti‐VLA‐2 mAb PIE6 was comparable on both collagens (25%±7.48% and 36.3%±0.94%, respectively; p<0.09). Immunohistochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA‐1+VLA‐2‐. While not directly applicable to MF, the demonstrated functions of VLA‐1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA‐1 integrins in epidermotropism in a small proportion of leukemic MF cells.

Aspergillus niger endocarditis in an immunocompetent patient: an unusual course

Aspergillus is an opportunistic nosocomial fungus generally associated with a high mortality rate.A niger has been rarely associated with infection, and most cases have occurred in patients who have recently undergone heart surgery or in immunocompromised patients. We present a case of an immunocompetent patient with A niger endocarditis which illustrates the difficulties in diagnosis and the possible insidious course of fungal endocarditis.

Polyarteritis Nodosa: A Report from Israel

BACKGROUND The clinical manifestations and outcome of all adult patients with polyarteritis nodosa (PAN), allocated during a 15-year period in the largest medical center in Israel, were examined. METHODS A retrospective analysis of patients with PAN who fulfilled the American College of Rheumatology (ACR) 1990 Classification Criteria and were either biopsy- or angiography-proven. RESULTS Nine patients were included in the report. The clinical and laboratory manifestations were similar to those in previous studies. All patients were treated with combinations of cyclophosphamide and corticosteroids. There were two (22%) deaths, 2 and 5 months after initiation of treatment in patients who probably had microscopic polyangiitis (MPA) rather than classical PAN. Considering the patients with a complete follow-up, 71% had a complete and long-term remission. Moreover, by exclusion of the two patients with probable MPA who died, all of the five patients with classical PAN were alive and well as of this writing. Two patients (22%) had a long history, since childhood, of familial Mediterranean fever (FMF). CONCLUSIONS The clinical presentation and course of PAN in Israeli patients is comparable with reports elsewhere. However, a distinction should be made between PAN and MPA. The present report emphasizes the good long-term prognosis of patients with typical PAN who are treated adequately. In addition, a possible association of PAN with FMF in Israeli patients is suggested.