Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients

OBJECTIVE: To assess the indications, efficacy, and tolerability of mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to other immunosuppressive therapy. METHODS: Records of 93 patients with SLE were retrospectively reviewed. Seven patients were excluded. The remaining 86 patients received other immunosuppressive drugs before MMF. Efficacy was measured by changes in daily oral prednisolone dose, European Consensus Lupus Activity Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive protein, and dsDNA antibody titer. In renal patients, changes in serum creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate (EDTA-GFR), and 24 hour urine protein excretion were also evaluated. RESULTS: Indications for MMF were mainly renal involvement (59% of patients), uncontrolled disease activity (14%), and other SLE related manifestations (13%). Overall, we found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA antibody titer. Renal patients (n = 35) showed a significant reduction in urinary 24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and EDTA-GFR showed no significant change during treatment. Thirty-seven patients (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14 (16.3%) patients due to side effects and 6 patients discontinued MMF because they achieved disease remission and were trying to conceive. MMF was stopped due to lack of efficacy in 12 patients. CONCLUSION: Our data suggest that MMF is a good therapeutic alternative for patients with SLE and renal involvement or refractory disease activity.     

Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus

OBJECTIVE: To investigate potential differences between childhood-onset and adult-onset systemic lupus erythematosus (SLE). METHODS: An inception cohort with childhood-onset SLE (n = 67) was compared with an inception cohort with adult-onset SLE (n = 131), each of whom was diagnosed between 1990 and 1998 and followed up until February 1999. Prospective information included data on medications, laboratory markers, and disease activity and damage as measured by the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), respectively. RESULTS: Eighty-five percent of patients with childhood-onset SLE and 88% of patients with adult-onset SLE were female; the mean duration of followup was 3.2 and 3.5 years, respectively. On average, the children had more-active disease than did the adults at the time of diagnosis and during followup. There was a higher incidence of renal disease in those with childhood-onset SLE (78% versus 52% in adults; P = 0.0005), and the adjusted mean SLEDAI renal score was higher in the children than in the adults (2.37 versus 0.82; P < 0.0001). Treatment with steroids (97% versus 72%; P < 0.0001) and immunosuppressive drugs (66% versus 37%; P = 0.0001) was used significantly more often in children with SLE. Four adult patients with SLE, but none of the children, died during the followup. At the end of the followup, the mean SDI scores in those with childhood-onset SLE were higher than those with adult-onset SLE (1.70 versus 0.76; P = 0.008). CONCLUSION: Children with childhood-onset SLE have more active disease at presentation and over time than do adults with SLE, especially active renal disease. Compared with adults with SLE, children receive more intensive drug therapy and accrue more damage, often related to steroid toxicity.     

Mycophenolate mofetil treatment in resistant myositis

OBJECTIVES: To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy. METHODS: Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose. RESULTS: The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03). CONCLUSION: Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.     

The clinical significance of iC3b neoantigen expression in plasma from patients with systemic lupus erythematosus

We studied the expression of an iC3b neoantigen (iC3b-NEO) in plasma from patients with systemic lupus erythematosus (SLE), by using a monoclonal antibody specific for iC3b/C3dg/C3d, to investigate the activation of the third component of complement in SLE. The plasma iC3b-NEO level in 40 untreated patients with active SLE was significantly higher than that in 36 normal subjects (mean +/- SD 31.5 +/- 13.9 micrograms/ml versus 12.3 +/- 3.3 micrograms/ml; P less than 0.001). The plasma iC3b-NEO level was highly correlated with clinical disease activity (tau = 0.62, P less than 0.0001), and it was the parameter most closely correlated with renal histologic activity in lupus nephritis (tau = 0.52, P less than 0.0001). Also, patients with diffuse proliferative lupus nephritis had the highest levels of plasma iC3b-NEO among all World Health Organization classes of lupus nephritis (P less than 0.01). We conclude that the plasma iC3b-NEO level is strongly associated with clinical disease activity and renal histologic activity in patients with SLE, and that plasma iC3b-NEO may be a sensitive and useful measure of complement activation in SLE.     

Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease

OBJECTIVE: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. METHODS: SLE patients (n=56) and healthy controls (n=18) were studied. All patients had quiescent disease (SLE disease activity indexor=40 against A/H3N2 (p=0.030) compared with the other patient groups. CONCLUSIONS: Influenza vaccination in SLE patients with quiescent disease is safe but is less effective than in controls. Use of azathioprine was associated with a trend to decreased vaccination efficacy.     

Skin manifestations of systemic lupus erythematosus refractory to multiple treatment modalities: poor results with mycophenolate mofetil

OBJECTIVE: Skin disease can be one of the most refractory clinical manifestations of systemic lupus erythematosus (SLE). The standard therapy consists of sunscreens, topical corticosteroids and antimalarials. However in difficult cases a variety of other drugs have been tried. Here we describe our clinical experience with mycophenolate mofetil (MMF) in patients with cutaneous manifestations of SLE. METHODS: Seven patients with SLE and skin involvement (including acute cutaneous lupus, subacute cutaneous lupus, discoid lupus erythematosus, vasculitis, urticarial rash and chilblain lupus) who had received treatment with MMF were included. The clinical characteristics, serologicalfindings and response to treatment were recalledfrom retrospective review of the files. RESULTS: Our results showed no response in 5 patients, partial response in 1 patient and initial response but skin flare whilst on MMF in 1 patient. The median dose of MMF was 2 g (range 2-3 g). Adverse events on MMF were mild, mainly gastrointestinal and occurred in 5 patients. No patients discontinued MMF due to adverse events. CONCLUSIONS: MMF appears not to be particularly effective in the treatment of skin disease in SLE. It should be noted that our group of patients had previously failed to respond to a median of 4 (range 2-10) different drugs used to treat SLE skin disease. Thus, the patients in the study could be considered at the severe end of skin disease spectrum.     

Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.     

B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus

OBJECTIVE: To determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood-onset systemic lupus erythematosus (SLE). METHODS: Seven patients (4 of whom were female), ages 7.7-16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2-week period, patients received two 750-mg/m2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high-dose oral corticosteroids. RESULTS: Patients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14-37) at baseline to a median score of 6 (range 4-11) at followup (P = 0.002). In 2 patients with severe multisystem and life-threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria. CONCLUSION: This open-label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.     

Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVE: Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis. METHODS: A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls. RESULTS: NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r >/= 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis. CONCLUSION: Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes.     

Tolerability of mycophenolate mofetil in patients with systemic lupus erythematosus

OBJECTIVE: To quantify the adverse events (AE) associated with mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE), to examine the relationship between AE and dosage of MMF, and to assess the overall tolerability of MMF in SLE patients. METHODS: A consecutive cohort of adults with SLE who received MMF between October 1996 and June 1999 was identified. Charts were reviewed for baseline data, AE, MMF dosing characteristics, and clinical response at baseline, 3 months, and at final followup or drug discontinuation. RESULTS: The 54 SLE patients were followed for a mean of 12.4 +/- 7.0 person-months. Baseline characteristics: 92.6% female, 72.2% white, mean age 38.3 years, and a mean of 9.6 years since diagnosis. Twenty-one of 54 patients (38.9%) had a total of 28 gastrointestinal AE. Twenty-four of 54 (44.4%) patients had a total of 37 infections, only one of which required hospitalization. Leukopenia occurred 3 times but never required dose adjustment. AE occurred at a similar rate at all MMF doses. Kaplan-Meier estimates show most drug discontinuation occurred in the first 2.5 months and 73% of patients were still on the drug at 12 months. Sixteen of 54 patients discontinued MMF because of AE (n = 9), lack of efficacy (n = 3), pregnancy (n = 2), and administrative reasons (n = 2). Clinical improvement in patients was noted with significant decreases in disease activity measured by the SLEDAI and prednisone dose at 3 months and at final followup. CONCLUSION: The majority of patients tolerated MMF. A range of doses was tolerated and associated with clinical improvement, suggesting that a flexible dosing schedule should be considered when using MMF in patients with SLE.     

狼疮肾炎终末期肾病患者尸体肾移植的临床观察

目的　探讨狼疮肾炎终末期肾病 (LN ESRD)患者行尸体肾移植手术的可行性及预后和狼疮活动的情况。方法　回顾性分析我院自 1972年开展肾移植手术以来 6例LN ESRD患者在透析时、术前及术后狼疮活动性指数 (SLEDAI)以及移植的时机、移植后免疫抑制剂的使用和人 /肾存活情况。结果　 6例皆为女性患者 ,皆因LN而出现ESRD。移植前皆接受慢性透析治疗 ,其中透析距移植的时间最短为 3个月 ,最长为 9年。移植后 3例用强的松、环孢素A和霉酚酸酯三联免疫抑制治疗 ,另 3例用泼尼松、环孢素A和硫唑嘌呤治疗。 6例患者有 5例存活至今 ,平均存活 (44± 34 )个月 ,最长为 85个月 ,最短为 4个月。 1例在移植后 4个月因高血压脑出血而死亡 ,死前肾功能正常 ,且无狼疮活动。移植术后 1周内移植肾功能皆恢复正常 ,无 1例因狼疮复发而致移植肾功能减退或丧失 ,其中带肾存活最长且肾功能的保持正常者已达 77个月。在慢性透析期间及移植术后无狼疮活动 (SLEDAI<9分 )。结论　肾移植是治疗LN ESRD成功而有效的手段 ,肾移植后狼疮复发率低。     

High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus

OBJECTIVE: High-dose chemotherapy followed by hematopoietic stem cell transplantation is increasingly being studied as a treatment for severe autoimmune disorders, such as systemic lupus erythematosus (SLE). High-dose cyclophosphamide, the foundation of virtually all conditioning regimens for stem cell transplantation, is not myeloablative; therefore, when high-dose cyclophosphamide is used alone, autografting, with its potential for reinfusing autoreactive effector cells, is not required. We undertook this study to investigate the safety and efficacy of high-dose cyclophosphamide without stem cell transplantation in refractory SLE. METHODS: We treated 14 patients with moderate-to-severe SLE that had been refractory to corticosteroids and one or more additional immunosuppressive drugs. All patients received 50 mg/kg of cyclophosphamide for 4 consecutive days followed by 5 microg/kg granulocyte colony-stimulating factor until the neutrophil count was 1 x 10(9)/liter for 2 consecutive days. Patients were followed up monthly for disease activity using the physician's global assessment, SLE Disease Activity Index, and assessment of functioning of involved organs. The Responder Index for Lupus Erythematosus was used to define partial or complete response. RESULTS: The median time to achieve a neutrophil count of 0.5 x 10(9)/liter was 14 days (range 11-22 days) after the last dose of cyclophosphamide. Patients required a median of 2 units (range 2-5) of packed red blood cells, and a median of 16 days (range 0-23 days) elapsed from the last dose of cyclophosphamide to the last platelet transfusion. There were no deaths or fungal infections. Significant improvements in physician's global assessment (mean difference 1.4; P < 0.0001), SLE Disease Activity Index (mean difference 4.1; P = 0.0039), and prednisone dosage (mean difference 14.9 mg/day; P = 0.002) were observed. Responses, including 5 durable complete responses, were observed in all organ systems (renal, central nervous system, and skin) with involvement that had led to patient enrollment. CONCLUSION: High-dose cyclophosphamide without stem cell transplantation leads to rapid hematopoietic reconstitution and has significant clinical benefit in patients with refractory SLE. Therefore, this approach deserves further study.     

Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial

OBJECTIVE: To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. METHODS: We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. RESULTS: Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced > or =50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. CONCLUSION: Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.     

High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients.

OBJECTIVE: Serum concentration of antibodies to C1q (C1qAb) has been reported to be elevated in a high percentage of patients with systemic lupus erythematosus (SLE). The associations of high C1qAb levels with different clinical manifestations and the activity of the disease, however, are not definitely understood. METHODS: We measured the levels of IgG type C1qAb in the sera of 137 patients with SLE using an ELISA method. RESULTS: Serum concentrations of C1qAb were found to be higher (p < 0.0001) in SLE patients than in healthy controls. High titer (> 66 AU/ml) C1qAb was found in 40/137 (29.2%) SLE patients, and 4/192 (2.1%) healthy controls (p < 0.0001). A strong negative correlation (R = -0.4, p < 0.0001) between the age of the patients and the C1qAb titers could be detected. C1qAb levels in clinically active SLE patients significantly (p < 0.0001) exceeded those measured in the sera of patients in the inactive stage of the disease. A significant positive correlation was detected between C1qAb levels and the laboratory activity markers (anti-DNA, low C3 level) of the disease. We found a significant negative correlation between levels of C1qAb and a negative acute phase protein, alpha2-HS-glycoprotein. Renal involvement was present in 11/40 (27.5%) and 11/97 (11%) of the patients with high and low titers of C1qAb, respectively (p = 0.038). The prevalence of other organ manifestations was, however, the same in the patients with or without high titer C1qAb. CONCLUSION: These findings indicate that C1qAb measurement is a useful method for detecting the activity of SLE and predicting renal manifestations, but not other organ involvement in the disease.     

Mycophenolate mofetil in diffuse cutaneous systemic sclerosis--a retrospective analysis

OBJECTIVES: We have assessed indications, duration and tolerability of treatment with mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc), and compared clinical outcome with a control cohort treated with other immunosuppressive drugs. METHODS: The clinical records of 109 patients treated with MMF and 63 control subjects receiving other immunosuppressive drugs were reviewed. Data covering a 5-yr period from commencement of treatment or until last assessment date were collected. RESULTS: MMF and control groups were well-matched in terms of basic demographic and clinical parameters. Treatment with MMF was very well tolerated. Of all patients, 12% experienced adverse reactions with gastrointestinal (GI) tract disturbances and infections being most frequent. MMF was discontinued due to disease stabilization in 9%, side effects in 8% and no effect on the disease activity in 14% of the patients. There was a significantly lower frequency of clinically significant pulmonary fibrosis in the MMF-treated cohort (P = 0.037) and significantly better 5-yr survival from disease onset and from commencement of treatment (P = 0.027 and P = 0.012, respectively). There was no significant difference between the two groups in terms of modified Rodnan skin score and forced vital capacity (FVC) change. CONCLUSIONS: MMF is very well tolerated and appears to be at least as effective as the other current therapies for dcSSc. Our results provide support for further evaluation of MMF in a prospective trial.     

Mycophenolate mofetil (CellCept): an alternative therapy for autoimmune inflammatory myopathy

OBJECTIVES: Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently being used for the prevention of renal allograft rejection. MMF is a specific inhibitor of lymphocytes and is well tolerated leading to its use in other autoimmune diseases. We have used MMF for the treatment of seven patients with inflammatory myopathy and are hereby reporting our results. CASE SERIES: All of our patients were females (age 17-65 yr). They were symptomatic upon presentation and met classification criteria for idiopathic inflammatory myopathy. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein as well as creatine kinase were significantly elevated in all the patients, indicating active disease. Corticosteroids were concomitantly being administered (20-60 mg/day of prednisone). Initial therapy with conventional immunosuppressives was either ineffective or had significant adverse effects leading to their discontinuation. MMF was started in doses of 500 mg twice a day and titrated up to 1 g twice a day. RESULTS: Our patients have exhibited an impressive serological response to therapy with MMF and six patients had a marked improvement in their weakness. One patient had incomplete improvement in her weakness and has required additional therapies. MMF has been well tolerated during the treatment period (12-36 months). CONCLUSION: A striking clinical and laboratory response of active myositis in six out of seven patients in this series illustrates that MMF can be effectively used in management of autoimmune inflammatory myopathy and may be a suitable alternative to the conventional immunosuppressive agents.     

Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus

OBJECTIVE: To report the first clinical experience with mycophenolate mofetil (MMF, CellCept) in: children with lupus nephritis. METHODS: Eleven children with various forms of lupus nephritis were treated with oral MMF at a mean dose of 22 mg/kg/day (range 17-42) for a mean of 9.8 months (range 3-17). All children received concomitant prednisone and 7/11 were taking concomitant hydroxychloroquine. Indications for MMF included treatment refractory nephritis despite high dose oral or IV prednisone, azathioprine, and/or cyclophosphamide. Treatment outcome was monitored through assessment of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, renal function, and serologic markers such as complement and anti dsDNA antibodies. RESULTS: While renal function normalized in 4/4 patients with membranous glomerulonephritis, little effect was observed in children with proliferative glomerulonephritis. Ten children experienced a marked reduction in SLEDAI score. Anti-dsDNA antibody and serum complement levels improved or remained stable in 80% of the children. Concomitant prednisone was decreased in 6/11 patients (55%) without deterioration of renal function. Adverse events, observed in 8 patients (73%), were not dose dependent, and included infections, leukopenia, nausea, pruritus, headache, and fatigue. CONCLUSION: MMF may represent a valuable alternative to traditional cytotoxic agents for children with class V lupus nephritis, but was less effective in attenuating disease progression in class IV glomerulonephritis. MMF had a steroid sparing effect and appeared to be effective in controlling serologic disease activity in pediatric onset SLE. Adverse events such as infections may limit its use and remain a concern.     

Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensus that any one of these agents is more effective than another. Mycophenolate mofetil (MMF) is an immunosuppressive drug proven to be effective in reducing renal allograft rejection as well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.     

Anti-nucleosome antibodies in patients with systemic lupus erythematosus of recent onset. Potential utility as a diagnostic tool and disease activity marker

OBJECTIVE: To compare the utility of anti-chromatin antibodies for the diagnosis of systemic lupus erythematosus (SLE) and as markers of disease activity. METHODS: We included 73 consecutive patients (62 female) with SLE (four or more ACR criteria) of recent onset (<1 yr since diagnosis). As control groups we included 130 healthy blood donors and 261 patients with 11 systemic autoimmune diseases (SAD). Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A venous blood sample was drawn to measure three anti-chromatin antibodies [anti-nucleosome (anti-NCS), anti-double-stranded DNA (anti-dsDNA) and anti-histones (anti-HST)] by enzyme-linked immunosorbent assay. RESULTS: The prevalence of anti-chromatin antibodies in SLE patients and healthy controls was 100 and 3% respectively for anti-NCS, 63 and 5% for anti-dsDNA, and 15 and 3% for anti-HST. Anti-NCS had a sensitivity of 100% and specificity of 97% for SLE diagnosis. When SLE and SAD patients were compared [excluding mixed connective tissue disease (MCTD)], the sensitivity of anti-NCS, anti-dsDNA and anti-HST antibodies for SLE diagnosis was 93, 71 and 40% respectively and the specificity was 97, 98 and 98%. Anti-chromatin antibodies were not useful in differentiating between SLE and MCTD patients. Anti-NCS antibodies showed the highest correlation with disease activity (r = 0.45, P < 0.0001), especially in patients negative for anti-dsDNA antibodies (r = 0.58, P = 0.001). Anti-NCS antibodies also showed strong association with renal damage (odds ratio 4.1, 95% confidence interval 1.2-13.6, P = 0.01). CONCLUSION: Anti-NCS antibodies could be a useful tool in the diagnosis and assessment of disease activity in SLE patients, especially in patients who are negative for anti-dsDNA antibodies.     

Analysis of lupus activity in end-stage renal disease treated by hemodialysis

OBJECTIVE: The activity of systemic lupus erythematosus (SLE) has been reported to decrease in patients who have developed end-stage renal disease (ESRD). However, extrarenal symptoms attributable to the disease activity are noted, especially during the first year of dialysis. We studied the clinical course and evaluate the disease activity of SLE in patients with ESRD on hemodialysis for more than 6 months. SUBJECT AND METHODS: Fourteen patients with SLE who had been initiated on maintenance dialysis at our center between 1982 and 1999 were examined retrospectively. Their clinical details, organ system manifestations, serologic profiles and immunosuppressive treatment regimens were reviewed. Patients with and without postdialysis flaras of SLE were compared statistically. RESULTS: Five patients exhibited 6 SLE flares under treatment with corticosteroids. Two flares occurred within the first year of the initiation of dialysis, and in 1 patient, aggravation of the disease activity was noted 98 months after the initiation of dialysis. Polyarthritis was noted in 5 cases and fever in 4 cases. The serum complement levels decreased in all 6 cases with relapse of SLE activity. Compared with the other 9 patients who did not exhibit SLE relapse, no significant differences were found in 5 patients who did with respect to the demographic and serologic features at the initiation of dialysis. CONCLUSION: We conclude that the disease activity does not always burn out in patients of SLE who show progression to ESRD. SLE flares can sometimes occur even after one year of the initiation of dialysis. SLE patients on dialysis should be carefully followed up by clinical and serological monitoring, and treated by appropriate immunosuppressive therapy.