Harry Spiera

Parkinsonism associated with Sjögren's syndrome: Three cases and a review of the literature

Sjögrens syndrome (SS) is a common multisystem autoimmune disorder. As with other autoimmune disorders such as systemic lupus erythematosus (SLE), SS has been associated with a wide range of neurologic abnormalities. Parkinsonism has been reported previously in five SS patients. We present three additional cases of SS with parkinsonism.

Renal transplantation in scleroderma.

Although the outcome of renal transplantation in patients with systemic lupus erythematosus (SLE) has been studied, there are few reports about the outcome of patients with systemic sclerosis who have undergone renal transplantation. We retrospectively collected data from the United Network for Organ Sharing (UNOS) Scientific Renal Transplant Registry from a 10-year period. From 1987 to 1997, 86 patients with systemic sclerosis who had renal transplantation were identified. Of these 86 patients, 70% were women, 86% were Caucasian, and the mean age at transplantation was 50.4 years. The overall mortality was 24% of the patient group; 44% (38/86) of renal grafts failed. First- through fifth-year graft survival rates were 62%, 60%, 57%, 50%, and 47%, respectively. The causes of graft failure could not be ascertained in 24 of 38 patients (63%). Among the known causes, 5 had acute rejection, 4 had chronic rejection, 3 had recurrence of scleroderma, and 1 each had infection and graft thrombosis. Immunosuppressive regimens used in the patients with systemic sclerosis consisted of antilymphocyte globulin in at least 25%. Sixty percent received a combination of steroids, azathioprine, and cyclosporine. The use of cyclosporine was not associated with either improvement of graft survival or an increased rate of graft failure. Graft survival at 5 years in patients with systemic sclerosis was comparable to that of patients with SLE who received renal transplantation, according to existent medical literature. Based upon these data, renal transplantation is as effective a treatment for restoring renal function in patients with systemic sclerosis as it is in patients with SLE. Those patients with systemic sclerosis whose renal function did not improve with angiotensin-converting enzyme (ACE)-inhibitor treatments after scleroderma renal crisis should be considered as transplant candidates. Although the data are incomplete, the use of cyclosporine may not confer the advantage of improving graft survival in patients with systemic sclerosis as compared with SLE patients.

Serologic factors in idiopathic diffuse interstitial pulmonary fibrosis

Abstract In nineteen patients with idiopathic diffuse interstitial pulmonary fibrosis, the serum of five (27 per cent) revealed latex-fixing macroglobulins. In four there were accompanying transient arthritic manifestations which were not readily classifiable. A comparable incidence of latex-fixing reactivity has been demonstrated in the serum of patients not afflicted with rheumatoid arthritis suggesting that this finding is not specific for any one disease. It is proposed that consideration of the diagnosis of rheumatoid lung be reserved for the rare combination of pulmonary fibrosis and unequivocal rheumatoid arthritis.

Autoantibodies to the Protein Core of Vascular Basement Membrane Heparan Sulfate Proteoglycan in Systemic Lupus Erythematosus

Vascular heparan sulfate proteoglycan (vHSPG) has an important role in the normal vasculature, including hemostasis, lipolysis and other vascular functions. These functions are mediated by both the glycosaminoglycan and protein core moieties of vHSPG. Autoimmunity to vHSPG has been demonstrated to play a role in vascular injury in animal models, and is present in patients with autoimmune vascular disease. However, most previous studies of human autoimmunity to vHSPG have only investigated heparan sulfate glycosaminoglycan epitopes. In the current investigations, autoantibodies to the protein core of vHSPG in sera from patients with systemic lupus erythematosus (SLE) were investigated. vHSPG protein core was prepared by chemical deglycosylation. Competitive immunoinhibition ELISA and immunoblotting immunoassays were established employing monoclonal antibodies to vHSPG protein core. SLE sera were demonstrated to contain IgG autoantibodies reactive with the vHSPG protein core by immunoblotting. Human autoantibodies to vHSPG protein core were not inhibited by heparan sulfate confirming their protein core reactivity. Competitive immunoinhibition studies employing a solid phase radioimmunoassay also confirmed the reactivity of human sera with vHPSG protein core. By ELISA, a significant increase in the occurrence of anti-vHSPG protein core antibodies was noted in SLE sera. While most previous investigations have demonstrated autoimmunity to heparan sulfate, the presence of IgG autoantibodies to vHSPG protein core demonstrates that the entire vHSPG proteoglycan is the target of autoimmunity in SLE.

Effect of halofuginone on the development of tight skin (TSK) syndrome.

The end point of pathogenic events in scleroderma is fibrosis of the skin and internal organs. Fibrosis in scleroderma results from the over synthesis and deposition of collagen in the connective tissue. The morbidity and mortality of the scleroderm is very high and presently there is no specific treatment. Halofuginone is a drug with great potential for the treatment of scleroderma since it inhibits the synthesis of collagen type I by fibroblasts. We have studied the in vivo effect of halofuginone in tight skin (TSK) mice that spontaneously develop a scleroderma-like disease due to a genetic defect. Our results demonstrate that halofuginone prevented the occurrence of skin sclerosis when administered to newborn mice and reduced cutaneous hyperplasia when administered in adult TSK mice. These effects correlated with a decreased number of cells synthesizing collagen gene transcripts and a reduction in the level of autoantibodies specific for human target antigens. These results indicate that halofuginone may have use as a therapeutic in the treatment of fibrotic disease.

Rheumatic symptoms and oral contraceptives.

Sir--We read with interest the report of Dr. Bole and his colleagues (Feb. 15 p. 323). Over the past three years we have seen 22 young women who from three months to one year after beginning oral contraceptives developed an illness characterized by arthritis arthralgia and myalgia. The objective joint swelling was usually limited to the hands. The only consistent laboratory abnormality was a moderately raised erythrocyte-sedimentation rate. Tests for rheumatoid factor and antinuclear antibodies and lupus-cell preparation were negative in all patients. On cessation of the oral contraceptive the signs and symptoms disappeared in from two to six weeks without further recurrence. We have been convinced that this syndrome has been induced by the oral contraceptives but were unable to prove that these cases did not represent patients with mild rheumatoid arthritis who went into spontaneous remission. Only two patients were re-challenged with oral contraceptives and both had a relapse of their symptoms which again subsided when the drug was withdrawn. Other patients were not re-challenged for fear of triggering an illness which would not be reversible. A prospective study such as Dr. Bole and his colleagues are contemplating is certainly necessary. On the basis of this experience we specifically inquire as to the use of oral contraceptives in all young women we see with rheumatic complaints. We also discourage our patients with known rheumatic disease from using oral contraceptives since a number of patients with rheumatoid arthritis have seemed to have had exacerbations after strating oral contraceptives. Of great interest is the hostility and anger expressed by patients who have been advised to stop taking oral contraceptives.(Full text)

Binding of synthetic double-stranded DNA by serum from patients with systemic lupus erythematosus: correlation with renal histology.

Detection of antibody to double-stranded DNA by direct binding assays has proved useful in clinical management of patients with systemic lupus erythematosus (SLE). Recent confusion regarding specificity of these antibodies for SLE appears to be due, at least in part, to contamination of natural DNA preparations with nondouble-stranded DNA antigens. Measurement of binding of a synthetic, self-complementary DNA copolymer (dAT) rather than of natural DNA (KB) has been shown to obviate some of these difficulties, apparently because of freedom of dAT from nondouble-stranded DNA antigens. Among the advantages found in this way was a higher degree of specificity of antibodies to double-stranded DNA for clinically-judged active lupus nephritis than had been suspected. Since activity of nephritis is difficult to assess clinically, histologic data were sought to confirm these observations. Thirty-two kidney specimens were examined by light and/or electron microscopy. The degree of histologic activity and the amount and location of glomerular electron-dense deposits were semiquantitated blindly. The binding of both dAT and KB DNA was measured by the ammonium sulfate method. Correlation with the amount of electron-defense deposits was highly significant for dAT binding and somewhat less so for KB DNA binding as determined by both parametric and nonparametric statistical methods. Significant correlation with histologic activity was found for dAT but not KB DNA binding. These results are consistent with previous data and suggest that dAT binding may provide a useful, noninvasive means of clinically assessing both nephritis activity and the intensity of glomerular immune-complex deposition as reflected by the amount of electron-dense deposits. If it can be confirmed that the latter provides long-term prognostic information, then dAT binding (and perhaps its reponse to therapy) may also prove of value in this regard.

Rheumatoid factors in an acute psychiatric population.

The existence of agglutinating substances reactive with autologous and isologous human gamma globulin (yG) has been recognized for some time. These substances were first found in patients with rheumatoid arthritis and were consequently termed rheumatoid factor (RF). It is now clear that rheumatoid factor is not specific for rheumatoid arthritis, but occurs in individuals with a wide variety of other diseases characterized by inflammation, infection, and/or granulomatous formation. Hepatitis, primary biliary cirrhosis, leprosy, syphilis, and subacute bacterial endocarditis are but a few of the other diseases unrelated to rheumatoid arthritis in which some degree ofRF activity has been observed. RF has been detected in a high proportion of aged individuals, and is known to occur occasionally in healthy younger persons. Experimentally, rheumatoid-like factor has been induced in rabbits after repeated immunization with various antigens. Since rheumatoid factors derived from various human sources share the ability to react with some form of yG immunoglobulin, they have been sometimes referred to as anti-yG factors. As part of a survey of the presence of rheumatoid factor in various populations, it was decided to examine patients newly admitted to an acute psychiatric voluntary hospital who were free of coexisting physical illness, known to be associated with RF, and who had not been subjected to long periods of institutional confinement just before testing. This study was originally prompted by the casual observation of transient RF activity in a patient during a period of severe depressive psychosis.

Eosinophilic temporal and systemic arteritis

We describe a 39-year-old patient with an unusual type of bilateral temporal arteritis characterized histologically by inflammation, diffuse eosinophilic infiltration, destruction of elastic tissue, and fibrosis. In addition, the patient had a history of systemic vasculitis, peripheral eosinophilia, eosinophilic lymphadenitis, and membranous glomerulonephritis. The patient has been followed up for 14 years and is well controlled on moderate doses of steroids. We propose that this patient suffers from an immune reaction to an unknown, possibly infectious, antigen.

Rheumatoid factor activity in heroin addicts on methadone maintenance.

It is now well known that rheumatoid factors (RF) or antigamma globulin antibodies are found in many individuals with a wide variety of diseases other than rheumatoid arthritis (Bartfeld, 1960, 1969; Oreskes and Spiera, 1966, 1967). In many of these diseases the presence of RF seems to be related to a previous or concurrent history of chronic antigenic stimulation. Examples of this include cases of subacute bacterial endocarditis (Williams and Kunkel, 1962) and tuberculosis (Singer, Plotz, Peralta, and Lyons, 1962), as well as diabetics on long-term insulin therapy (Oreskes and Spiera, 1973). Similarly, RF is present in patients who have received multiple transfusions (Vierucci, 1965) or vaccinations (Aho, Konttinen, Rajasalmi, and Wager, 1962). Tuffanelli (1968), Nickerson, Williams, Boxmeyer, and Quie (1970), and Ryan, Parker, and Williams (1972) have reported significant levels of RF activity in heroin addicts. Typically, individuals who are addicted to heroin repeatedly inject themselves with heroin which may also contain other foreign substances. It is a plausible view that heroin or its adulterants are antigenic, or may become antigenic by forming complexes with endogenous protein. Therefore, one might expect in many of these individuals production of antibodies to these antigens. Resultant antigen-antibody complexes could in turn serve as the stimulus for RF production. An alternative possibility is that RF in heroin addicts is in some way related to the liver dysfunction commonly seen in such individuals. Correlation of RF activity and liver disease has been frequently reported (Bartfeld, 1969). The purpose of the present study was to follow the course ofRF in heroin-dependent persons on methadone maintenance to obtain additional information regarding the pathogenic mechanism of RF production.