John L. Decker

Increased Risk of Lymphoma in Sicca Syndrome

The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkins lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenströms macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.

Immune Interferon in the Circulation of Patients with Autoimmune Disease

The observation that type II, or immune, interferon could be produced by peripheral-blood leukocytes in vitro on an immune-specific basis suggested that it also might be produced in vivo in various autoimmune disorders. We found immune interferon in the serums of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma and Sjögrens syndrome. Among 28 patients with systemic lupus erythematosus, 71 per cent of those with active and 21 per cent of those with inactive disease showed interferon in their serums. Serial serum samples showed a good correlation between interferon titers and disease activity. Moreover, interferon titers correlated positively with antibodies to DNA and negatively with serum levels of the third component of complement. It is possible that the production of interferon may contribute to immunologic aberrations in auto-immune diseases and also protect the already compromised host from viral infections.

Prognostic factors in lupus nephritis: Contribution of renal histologic data

The predictive value of laboratory results and renal histologic data was examined in 102 patients upon entry into prospective, randomized, therapeutic trials of lupus nephritis. Three clinical features at the time of entry into the study were individually associated with increased rates of renal failure: age less than 24 years, male gender, and an elevated serum creatinine level. Subjects with diffuse proliferative or membranoproliferative glomerulonephritis were at a modest but significantly increased risk for the development of end-stage renal disease compared with patients with other classes of lupus nephritis. Semiquantitative scores of histologic features (specified by activity and chronicity indexes) identified subgroups of patients with comparatively high renal failure rates. To address the controversial issue of whether renal histologic data significantly improve the outcome predictions in patients with lupus nephritis, multivariate survival models were generated, permitting simultaneous consideration of multiple prognostic factors. Outcome predictions based on the strongest clinical predictors (age, sex, and serum creatinine level) were significantly enhanced by the addition of activity and chronicity indexes. Only age and chronicity index contributed significantly to the five-variable model and together constituted a two-variable model, the predictions of which were similar to observed outcomes. In the context of the highly significant prognostic indicators (age and chronicity index), immunosuppressive agents appeared to provide a slight therapeutic advantage over oral corticosteroids alone.

Measurement of serum DNA-binding activity in systemic lupus erythematosus.

Abstract Antibodies to DNA were demonstrated in the serums of patients with systemic lupus erythematosus (SLE) by ammonium sulfate precipitation. DNA is soluble in 50 per cent saturated ammonium sulfate, whereas immunoglobulins and immunoglobulin-bound DNA are insoluble. When ammonium sulfate is added to a mixture of radioactive DNA and serum, the precipitate contains radioactivity if DNA is bound to immunoglobulins. Abnormal binding was found in serum of 75 per cent of unselected patients with SLE, 25 per cent with Sjogrens syndrome, 5 per cent with related disease and 2 per cent of normal subjects. All of 52 selected SLE serums with positive, as well as 21 of 32 SLE serums with negative, complement-fixation tests for anti-DNA antibodies had abnormal binding. Binding activity was associated with immunoglobulin G of serum. High binding values were seen chiefly in patients with active SLE renal disease; marked reductions accompanied clinical improvement. The test overcomes problems inherent in other metho...

B-lymphocyte alloantigens associated with systemic lupus erythematosus.

We examined B-lymphocyte alloantigens in 41 patients with systemic lupus erythematosus and 184 controls, using a panel of 47 pregnancy serums, and compared reaction frequencies of individual serums. One serum, la-715, reacted with B lymphocytes from 75.6 per cent of patients and 14.1 per cent of controls (Pc less than 0.005, relative risk 18.8). Twenty-eight of the patients were also typed with a panel of HLA-D-related serums from the Seventh International Histocompatibility Workshop, HLA-DRw types assigned, and compared to 490 Workshop controls. Both HLA-DRw2 (57.1 per cent vs. 26.4 per cent, Pc less than 0.004) and HLA-DRw3 (46.4 per cent vs. 22.2 per cent, Pc less than 0.03) were increased in systemic lupus erythematosus. This study demonstrates that select B-lymphocyte alloantigens, which are controlled by genes in the major histocompatibility complex, are present in increased frequency in systemic lupus erythematosus.

Systemic Lupus Erythematosus: Evolving Concepts

Abstract Systemic lupus erythematosus, a disease of unknown cause and protean manifestations, continues to excite substantial investigational interest. These papers bring together recent advances i...

Effect of Treatment on the Evolution of Renal Abnormalities in Lupus Nephritis

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis

In this restrospective study we review the clinical features of patients with the sicca syndrome in the presence and absence of rheumatoid arthritis. All patients were followed at the National Institutes of Health for at least five years after the diagnosis of sicca syndrome was established. Twenty-two patients had sicca syndrome alone, and 21 patients had definite rheumatoid arthritis and the sicca syndrome. Rheumatoid arthritis tended to precede the developement of sicca syndrome. The mean age at diagnosis of sicca syndrome is the same in both groups. No significant differences in serum innumoglobulins, the third component of complement (C3), rheumatoid factor titer and salivary histopathology were found. However, the clinical features were quite distinct. Patients with sicca syndrome alone had a significantly greater frequency of recurrent parotitis, Raynauds phenomenon, purpura, lymphadenopathy, myositis and renal involvement. The clinical characteristics of these two groups coupled with the known serologic and genetic differences suggest that sicca syndrome alone is a distinct pathologic entity.

Cyclophosphamide in Lupus Nephritis: A Controlled Trial

Abstract Thirteen women with lupus nephritis were hospitalized for a 10-week double-blind therapeutic trial comparing oral cyclophosphamide with placebo. Concurrent corticosteroid therapy, up to 30...

Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis.

The bladder complications of 54 patients treated with oral cyclophosphamide for systemic lupus erythematosus (43) or rheumatoid arthritis (11) were reviewed. During an observation period of 241 patient years, we saw seven cases of acute hemorrhagic cystitis and two cases of transitional cell carcinoma of the bladder. Bladder carcinoma was identified 28 and 60 months after withdrawal of the drug and resulted in the death of one patient. The late-occurring serious toxicities of cyclophosphamide should limit the use of the drug in the treatment of nonmalignant inflammatory rheumatic conditions.