Biomedical subjects
Publications and source records attributed to D J Wallace.
Apheresis is an innovative, expensive method for treating serious complications of refractory rheumatic disease and may be useful in selected cases. Technologic improvements which will increase our ability to remove plasma fractions and/or lymphocyte subsets are the object of study and may alter the current indications for performing apheresis, as well as increasing our basic knowledge of the disease process.
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An attempt is made to see if any correlation exists between the prevalence of 13 selected rheumatic diseases and the number of literature entries concerning these disorders in 1974 and 1983. Entries on systemic lupus are broken down in detail. It is concluded that interest in autoimmune diseases, especially their immunology, appears healthy. Lower morbidity disorders with a large prevalence (osteoarthritis, fibrositis, gout) may be disproportionately under-investigated. Whether any correlation between funding levels and literature entries can be made is speculative.
Eight patients with Functional Class III, seropositive, erosive rheumatoid arthritis unresponsive to remittive drugs each underwent nine aphereses over 3 weeks. Four had a 40-ml/kg plasma exchange and four others had a 40-ml/kg plasma exchange plus a mean 5.67 X 10(9) lymphocyte depletion. Both groups appeared to improve clinically. T and B cell counts and OK T4 and OK T8 ratios decreased in the lymphoplasmapheresis group. Phytohemagglutinin stimulation decreased in lymphoplasmapheresis and increased in plasmapheresis patients with significant comparisons (p = 0.02). These findings confirm and extend previous work. Plasmapheresis and lymphoplasmapheresis appear to have fundamentally different actions on lymphocyte function.
Therapeutic apheresis is a relatively new modality. Its absolute indications are few and include hyperviscosity syndrome, cryoglobulinemia, thrombotic thrombocytopenic purpura, Goodpasture's syndrome, and life-threatening complications of immunologic disorders refractory to conventional management. The use of apheresis in most of the other disorders discussed in this monograph is experimental and should not be employed unless all the mitigating therapeutic considerations clearly suggest an overwhelming advantage of apheresis. The promise of apheresis is much greater than its current use, and the research applications of specific component separation and antibody removal are of great importance. It is hoped that these new developments will shortly make current devices obsolete and improve the clinical management of patients as well as increase our knowledge of disease etiopathogenesis.
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Cryofiltration, a new technique for on-line plasma separation and its treatment by cold filtration, enables the selective removal of immune complexes and eliminates the need for replacement proteins. Fifteen patients with rheumatoid arthritis were treated for nine to 10 consecutive sessions over a three- to five-week period. Circulating immune complexes decreased by an average of 78 percent and rheumatoid factor by 32 percent. This was accompanied by significant clinical improvement in morning stiffness, articular index, 50-foot walking time, grip strength, and target joint circumference. Cryofiltration might thus be beneficial for a subgroup of rheumatoid arthritis patients in whom conventional therapy has failed.
Five patients with erosive rheumatoid arthritis (RA) who had previously experienced a favorable response to lymphoplasmapheresis were treated with cryapheresis. Cryapheresis was performed 9 times in 3 weeks using a membrane filtration device that selectively removes plasma proteins with molecular weights greater than 100,000 daltons. Four of the 5 patients so treated improved clinically. The membranes selectively removed more immunoglobulins and complement components that were part of circulating immune complexes than those that were not. Plasma or albumin replacement was not necessary in these patients. Cryapheresis might be a safe and effective technology in treating patients with refractory RA.
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Lupus nephritis with nephrotic syndrome is one of the most serious complications of systemic lupus erythematosus. Six female patients with systemic lupus and nephrotic syndrome, refractory to immunosuppressive drug therapy, received 15-20 exchange plasmaphereses. One patient, treated concurrently with high-dose steroids, showed temporary improvement, and five patients, treated concurrently with steroids and either cyclophosphamide or azathioprine, had long-term remissions. Plasmapheresis is a promising therapeutic modality in cases of refractory lupus nephritis with nephrotic syndrome.
Nephritis developed in 230 of 609 private patients with systemic lupus erythematosus (SLE) (38 percent) followed up from 1950 to 1980. Eighty-seven percent of patients with nephritis were female; 71 percent were Caucasian. They were observed a mean of 10 years. Five- and 10-year survival rates were 80 percent and 65 percent, with improvement to 86 percent and 76 percent in the last decade. Normalization of urinary sediment and protein levels, blood pressure and serum albumin levels correlated with improved survival and tended to occur during the first year. Life-threatening complications of SLE were more common after the onset of nephritis but decreased as renal function worsened. Infection was the most frequent cause of death in the last decade. Forty-four patients received nitrogen mustard; 55 percent of the courses were followed by significant improvement in renal function and reduced steroid dosage. Control of the disease was associated with improved long-term survival of patients with SLE.
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Six hundred nine private patients with systemic lupus erythematosus were followed up for a mean of ten years. Ninety percent were female; 79% were white. Three hundred sixty-nine received diagnosis before 1970, and 234 after. Three hundred seventy-nine did not have nephritis; 230 did. The overall ten-year survival was 79% (87% without nephritis, 65% with nephritis). Male patients did consistently worse than female patients. No overall white vs nonwhite difference was noted. The presence of nephrotic syndrome at the onset of nephritis was a poor prognostic sign, but its development later was not. Patients younger than 16 years without nephritis have an excellent prognosis. One hundred twenty-eight patients died (82 with nephritis, 46 without nephritis). The most common causes of death were renal disease and sepsis. Improved survival of this series may reflect closer follow-up, better nutritional status, and treatment at earlier stages of disease.
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Evidence developed over the years has suggested that lymphocyte depletion and removal of plasma factors can ameliorate rheumatoid arthritis. In our studies of 40 patients, a subset of patients that respond best to 20 therapeutic lymphoplasmapheresis over 11 weeks has emerged. These are functional Class III patients with seropositive, erosive progressive disease who have little deformity. They must be on long-acting agents or cytotoxic drugs during pheresis to prevent antibody rebound. Other studies have since confirmed our work. The major side effects of pheresis are elucidated. Technologic developments will enable selective pheresis procedures to be in widespread use within a few years.
Twenty-two patients with rheumatoid arthritis, 3 with seronegative juvenile rheumatoid arthritis, 4 with systemic lupus erythematosus, and 4 with psoriatic arthritis have undergone therapeutic pheresis at our institution over the last 3 yr. Lymphoplasmapheresis appears to be the most effective form of pheresis in treating rheumatoid arthritis. After achieving a remission with 20 treatments performed in 11 wk, a flare may be preventable by pheresing patients 3 times a week every 6 wk provided the patient is on a concomitant, long-acting agent. Therapeutic pheresis has been disappointing in seronegative juvenile rheumatoid arthritis. Life-threatening complications of systemic lupus erythematosus may respond dramatically to pheresis. In treating less severe disease on a long-term basis, pheresis has demonstrated excellent steroid sparing properties. Nonspondylytic psoriatic arthritis responds slowly to pheresis, but arthritic remissions may be prolonged, even though skin response is variable. Experience in the use of pheresis for treating these diseases has allowed for the development of criteria for deciding whether to institute such therapy as an adjunct to more standard modes of treatment for individual patients. Also, a variety of "technical" factors can influence the outcome of therapy, and these must be managed appropriately. Therapeutic pheresis is a promising tool for investigating and treating rheumatic diseases.