Remission of systematic lupus erythematosus.

The occurrence and characteristics of remissions in patients with systematic lupus erythematosus (SLE) have not been determined. We therefore studied this in a cohort of 667 patients and found that 156 patients had achieved at least 1 period of 1 year or more of treatment-free clinical remission. This represents an incidence density of 0.028 new cases/person/year. Remission occurred within the first 2 years of disease in 62 patients. The mean duration of first remission was 4.6 years (range, 1-21 yr), and 81 patients were still in the initial remission up until cutoff time. Half of the remaining 75 patients who flared after achieving remission have not entered again in remission. Twenty-six of the 38 patients who did remained in remission, and the remaining 12 had subsequent flares and remissions. Treatment-free remission accounted for a mean of 5.8 years, corresponding to half the time of follow-up. Remission was not limited to patients with mild disease: at least 41 patients achieved remission despite renal involvement, 19 had had neuropsychiatric lupus, 15 had had thrombocytopenia, and 8 had had hemolytic anemia. We also found that the longer the time lapse between the initial manifestation and the diagnosis of SLE, the less likely it was for a patient to enter into remission. There was a continuous increase in likelihood of achieving a first remission from the beginning of disease up to 30 years of disease duration, when it reached 70%. Patients who achieved remission had increased survival, independently of the effect of other disease manifestations that cause increased mortality. We conclude that a significant proportion of patients with SLE, including those with severe organ involvement, may become symptom-free and in need of no more medication, perhaps indefinitely. Our findings support the notion that, in general, SLE is a more benign disease than previously considered.

Influence of the antiphospholipid syndrome in the survival of patients with systemic lupus erythematosus.

OBJECTIVE: To determine prognostic factors for mortality in a cohort of 667 patients with systemic lupus erythematosus (SLE) including those variables associated with the presence of antiphospholipid antibodies (aPL) as well as antiphospholipid syndrome (APS) itself. METHODS: Analysis of the cohort under a nested case control design by means of Cox proportional hazards regression with and without stepwise method. RESULTS: During the 2039 person-years of followup, there were 49 deaths (cases). Thrombocytopenia, arterial occlusions, and hemolytic anemia were the aPL related manifestations that were associated with decreased survival in univariate analyses. The first 2 were also selected among risk factors for mortality in stepwise Cox multivariate analysis. The syndrome itself was also associated with increased mortality rates, independently of other variables. CONCLUSION: APS is among the variables that confer decreased survival on patients with SLE. This decreased survival is due to some (e.g., thrombocytopenia or arterial occlusions), but not all, of the manifestations of APS.

Influence of disease duration, continued followup and further antiphospholipid testing on the frequency and classification category of antiphospholipid syndrome in a cohort of patients with systemic lupus erythematosus.

In an earlier study of a cohort of 667 patients with systemic lupus erythematosus (SLE) followed for 7.5 months with mean antiphospholipid (aPL) testing 2.5 times, we found a 10% prevalence of definite antiphospholipid syndrome (APS) (2 clinical manifestations and high aPL levels). To determine if more followup and aPL testing increased such prevalence we restudied the cohort after a mean followup of 3.1 years and a mean aPL testing of 5.6 times and found a 15% prevalence of definite APS. Another 21% of patients with SLE had probable APS with either high titers of aPL but only one clinical manifestation or low titers with 2 clinical manifestations. The prevalence of high titer positivity of aPL (IgG and/or IgM isotype) reached 41%. One aPL related feature that increased significantly was livedo reticularis possibly from increased awareness. Factors that influenced significantly the mobility upwards in APS category were more pregnancies and further aPL testing. Conversely, immunosuppressive treatment decreased higher aPL levels. The large number of patients with long disease duration in our cohort showed that the maximum prevalence of definite APS is reached after 15-18 years and is 23%. This might be the highest prevalence of definite APS within SLE.

Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus.

Ten percent of 667 consecutive systemic lupus erythematosus (SLE) patients were considered to have definite antiphospholipid syndrome (aPLS) because they had two or more antiphospholipid (aPL)-related clinical manifestations and aPL titers more than 5 SD above the mean of normal controls. Another 14% had either one aPL-related manifestation but high titers of the antibody or two manifestations and low aPL titers (probable aPLS). One fourth of the patients had no manifestations but high titers, one manifestation and low titers, or two or more manifestations and negative aPL titers ("doubtful" aPLS); the other half were considered negative for aPLS. In patients with high-titer aPL, the number of aPL-related manifestations was influenced by disease duration and number of pregnancies, indicating potential mobility of category with time or with risk of recurrent pregnancy loss. Patients with two or more manifestations but variable aPL levels differed in immunosuppressive treatment and in the number of times they had been tested, indicating potential mobility of category with lower treatment and/or further aPL testing. Patients with definite aPLS had increased risk of cutaneous vasculitis, peripheral neuropathy, seizures, psychosis, transient ischemic attacks, and leukopenia. In 11 of 52 SLE patients with definite aPLS the initial manifestation was related to aPL, and in 16 it concurred with an unrelated one. Only two patients fulfilled criteria for aPLS before having other evidence of SLE. The authors conclude that aPLS occurring within SLE is part of the disease rather than an associated condition and propose the use of definite and probable classification categories. These criteria, with appropriate follow-up and clinical and serological exclusion clauses for potential primary conditions, could also be applied to primary aPLS.

Decrease in serum antiphospholipid antibody levels upon development of nephrotic syndrome in patients with systemic lupus erythematosus: relationship to urinary loss of IgG and other factors.

PURPOSE: Having observed a decrease in antiphospholipid antibodies (aPL) upon the development of nephrotic syndrome, as well as a negative association between nephrotic syndrome and secondary antiphospholipid syndrome, in patients with systemic lupus erythematosus (SLE), we sought to determine if this could be due to urinary loss of aPL and/or other factors. SUBJECTS AND METHODS: IgG and IgM aPL as well as other autoantibodies were studied by enzyme-linked immunosorbent assay with cardiolipin as antigen in serum and urine from six patients with SLE who had elevated serum aPL levels and developed nephrotic syndrome (cases). For controls, we studied: (1) three SLE patients with nephrotic syndrome but low aPL levels; (2) three patients with non-SLE nephrotic syndrome; (3) three SLE patients with high-titer aPL but no proteinuria; and (4) 10 healthy volunteers. RESULTS: We found urinary IgG, but no IgM, aPL in all cases and in one control from Group 2. Serum IgG aPL had gradually decreased after the development of nephrotic syndrome and had become normal. IgM aPL had also decreased in the four patients who had elevated levels, having reached normal levels at the time of the study in two. There was an apparent correlation between serum and urine IgG aPL levels but not between urinary IgG aPL and total proteinuria. By Farr's method, we found no urinary anti-DNA despite high serum titers in three cases. The two cases and one of the controls in Group 1 who had serum antibodies to extractable antigens also had these antibodies in the urine. CONCLUSION: Urinary loss of IgG aPL during nephrotic syndrome does not completely explain the reduction in serum aPL, since IgM also decreases. There could also be decreased synthesis and/or increased catabolism of immunoglobulins.