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PubMed2004

Intravenous cyclophosphamide--resistant systemic lupus erythematosus in Arizona.

Systemic lupus erythematosus (SLE) tends to be severe and to have a variable response in childhood. We undertook this retrospective study to assess response rates and outcome in 14 children with SLE. Mean age at onset was 12.8+/-3.1 years. Ten patients were female and 4 were male, and 12 patients (86%) were Hispanic. Creatinine clearance prior to therapy was 104+/-36 ml/min. All had hematuria and proteinuria with a protein/creatinine ratio of 3.9+/-4.8. WHO classification of renal biopsies revealed class IV in 64%, class III in 21%, and class V in 14%. Patients were treated with 6-monthly pulses of intravenous cyclophosphamide (IVCY) followed by longer-duration pulses. The mean duration of follow-up was 3.7+/-3.3 years. Of the 14 patients, 3 (21%) achieved systemic remission but all relapsed subsequently; 7 of 14 achieved renal remission, although 6 relapsed. Six (42%) had adverse outcomes, defined by death, dialysis, or need for bone marrow transplant. All 6 had failed 6 months of IVCY, suggesting that patients who demonstrate resistance to initial IVCY therapy have an unfavorable outcome and a high likelihood of complications. In summary, we report a poor response to standard therapeutic protocols with higher relapse rates, as well as significant adverse outcomes.

Adolescent↗

PubMed1999

Cytokines in the pathogenesis of systemic lupus erythematosus.

Cytokines, chemokines, and growth factors are overexpressed by renal parenchymal cells and by infiltrating mononuclear cells in human and experimental lupus nephritis. The importance of cytokines in the pathogenesis of lupus nephritis has been established using spontaneous mouse models of systemic lupus erythematosus (SLE). The actions of these cytokines are complex. There is a growing appreciation that the cytokine level and stage of kidney disease determines whether cytokine protects or promotes further tissue injury. This article identifies potential therapeutic targets and strategies that might halt progressive renal injury in patients with SLE.

Animals↗

PubMed1993

Systemic lupus erythematosus evolving into systemic vasculitis: a report of five cases.

Five patients with systemic lupus erythematosus are described who developed the disease in their second or third decade. The pattern of their disease then changed markedly and they developed the clinical features of a systemic vasculitis. The possible explanations for this transition of one connective tissue disease to another is discussed.

Adolescent↗

PubMed2001

Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study.

BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group. METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified. RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients. CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.

Adolescent↗

PubMed2006

[A case report of childhood systemic lupus erythematosus complicated with lupus cystitis].

The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.

Adolescent↗

PubMed1987

Silent renal disease in systemic lupus erythematosus.

Several recent studies have focused on the discrepancy between lupus nephropathy and clinical renal involvement and, consequently, question the relevance of renal biopsy in these patients. We analyze the clinical characteristics, histological renal findings and subsequent course of patients with silent renal disease. Renal biopsy was performed in 15 patients with systemic lupus erythematosus (SLE) who had no clinical signs of renal involvement (no urinary sediment abnormalities, absence of proteinuria and serum creatinine less than 1.3 mg/dl). All biopsies were classified according to a modified classification proposed by the WHO. Six cases (40%) showed no histological or immunofluorescence changes (type I), 7 (47%) had mesangial nephropathy (3 type IIa and 4 type IIb) and 2 (13%) had focal proliferative glomerulonephritis (type III). None of the patients had previous evidence of neurological abnormalities. Patients with type I only had arthritis, skin lesions and Raynaud's phenomenon. By contrast, 7 patients with histological renal involvement had serositis or hemolytic anemia. All cases with silent nephropathy were treated with steroids and showed a benign clinical course with stable renal function and absence of urinary abnormalities during follow-up. We concluded that in the absence of clinical renal abnormalities, renal involvement is not uncommon in SLE. We believe that a renal biopsy should be performed mainly in those SLE patients presenting with clinical manifestations other than arthritis or cutaneous lesions since this policy may allow detection of significant silent renal injury.

Adolescent↗

PubMed1998

Double-negative (CD4-CD8-) TCRalphabeta+ cells in patients with systemic lupus erythematosus.

Massive accumulation of CD4-CD8-TCRalphabeta+ cells in secondary lymphoid organs is characteristic of lupus-prone MRL/lpr mice. However, the role of these double negative T cells (DNT) in human lupus patients receive only limited attention. Herein, we investigate the frequency of DNT in the peripheral blood mononuclear cells of forty seven Chinese patients with systemic lupus erythematosus (SLE) and forty four normal individuals. DNT were measured with dual-fluorescence flow cytometry. The results showed that DNT only constituted a very minor subset of lymphocytes both in patients and normals, it normally did not exceed 2% of the lymphocyte population. Compared with normal subjects, patients with SLE had slightly increased levels of DNT within the total lymphocyte population (0.66+/-0.45% vs 0.51+/-0.33%) or within TCRalphabeta+ population (1.14+/-0.88% vs 0.88+/-0.54%). The difference, however, did not reach statistical significance. The levels of DNT correlated neither with the titers of anti-DNA antibodies in sera nor with the presence of active and severe lupus nephritis in SLE patients. Longitudinal follow-up of six patients at the stages of active and inactive nephritis revealed similar levels of DNT in the same individual. The preliminary results suggest that circulating DNT do not appear to play a critical role in Chinese patients with SLE.

Adolescent↗

PubMed2007

[Revision of the recommendations of the Commission on Pharmacotherapy of the German Society for Rheumatology. Comment on the use of mycophenolic acid for systemic lupus erythematosus].

According to the NIH scheme, the "evidence based medicine" standard in the treatment of severe proliferative lupus-nephritis is cyclophosphamide in combination with steroids. Undesired effects, therapy resistance, and deficient long-term effects underscore the necessity for the development of alternative therapies for the treatment of organ involvement. Mycophenolate mofetil (MMF) possesses the potential to decisively improve the therapeutic possibilities for systemic lupus erythematosus (SLE). On the basis of the available data, MMF represents an alternative to the current standard therapies for severe lupus-nephritises and shows less toxicity. MMF is also effective in patients with other manifestations refractory to conventional therapy. Questions remain unanswered on the optimal dosage and possible reduction in cases of remission. In addition, the duration of maintenance therapy is unclear. Therefore, large, prospective, randomized clinical studies in the treatment of lupus-nephritis with a sufficiently long follow-up phase are underway.

Drug Therapy, Combination↗

PubMedDate not supplied

Random number generation evaluation in patients with systemic lupus erythematosus indicates a heterogeneous nature of central nervous system vulnerability.

OBJECTIVE: To evaluate the vulnerability of the central nervous system (CNS) in patients with systemic lupus erythematosus (SLE). METHODS: Forty-eight patients with SLE, 58 with schizophrenia in remission and 39 healthy controls were enrolled in the study. Patients vocally generated 100 numbers in a random fashion, using numbers 0 to 9, and were evaluated with seriality scores. Patients with SLE were subgrouped according to differences in the presence of Raynaud's phenomenon, anti-phospholipid antibody, lupus activity, and a history of neuropsychiatric (NP) lupus, and these patients were also evaluated by comparison with their counterparts. RESULTS: In general, patients with SLE showed lower seriality scores than patients with schizophrenia, and higher seriality scores than normal controls. The scores of the patients with a history of NP lupus matched those with schizophrenia, and the scores of never having NP lupus matched those of the healthy controls. CONCLUSIONS: CNS vulnerability may be prolonged in patients who have a history of NP lupus even when they appear to be in normal NP status. The damage in random number generation (RNG) observed in patients with a history of NP lupus seemed equal to that found in those with schizophrenia, whereas those patients never having NP lupus appeared to be equal to the controls. The current study suggests a heterogeneous nature of SLE and prolonged damage, especially in CNS vulnerability, when evaluating with RNG.

Adult↗

PubMed1993

Predictive value of IgG autoantibodies against C1q for nephritis in systemic lupus erythematosus.

OBJECTIVES: Antibodies against C1q (C1qAb) have been demonstrated in the serum of patients with several immune complex diseases. Patients, particularly those with lupus nephritis, were found to have increased serum titres of IgG C1qAb in a cross-sectional analysis. In the present prospective study correlations were sought between serum titres of IgG C1qAb and clinical as well as laboratory parameters of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Titres of IgG C1qAb in the serum of 68 SLE patients were measured serially during a three year period. At the same time clinical and laboratory parameters of disease activity were assessed. RESULTS: Increased titres of IgG C1qAb were found in the serum of 56% of SLE patients during the study. Significant correlations were found between increased titres of IgG C1qAb and renal involvement. Clinical signs of renal involvement were found to be associated with significant increases of serum titres of IgG C1qAb in the six months preceding this appearance. Fifty per cent of the increases in serum titres of IgG C1qAb were followed by the development of renal involvement. Elevated serum titres of IgG C1qAb were especially related to proliferative forms of glomerulonephritis. Furthermore, significant correlations were found between serum titres of IgG C1qAb and serum levels of immune complexes, levels of complement components, and titres of antibodies to DNA. CONCLUSIONS: The results suggest that IgG C1qAb play a pathogenic role in the development of lupus nephritis and that serial measurement of serum titres of IgG C1qAb is useful in the management of SLE patients.

Adolescent↗

PubMed2006

Alpha-actinin-binding antibodies in relation to systemic lupus erythematosus and lupus nephritis.

This study investigated the overall clinical impact of anti-alpha-actinin antibodies in patients with pre-selected autoimmune diseases and in a random group of anti-nuclear antibody (ANA)-positive individuals. The relation of anti-alpha-actinin antibodies with lupus nephritis and anti-double-stranded DNA (anti-dsDNA) antibodies represented a particular focus for the study. Using a cross-sectional design, the presence of antibodies to alpha-actinin was studied in selected groups, classified according to the relevant American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) (n = 99), rheumatoid arthritis (RA) (n = 68), Wegener's granulomatosis (WG) (n = 85), and fibromyalgia (FM) (n = 29), and in a random group of ANA-positive individuals (n = 142). Renal disease was defined as (increased) proteinuria with haematuria or presence of cellular casts. Sera from SLE, RA, and Sjøgren's syndrome (SS) patients had significantly higher levels of anti-alpha-actinin antibodies than the other patient groups. Using the geometric mean (+/- 2 standard deviations) in FM patients as the upper cutoff, 20% of SLE patients, 12% of RA patients, 4% of SS patients, and none of the WG patients were positive for anti-alpha-actinin antibodies. Within the SLE cohort, anti-alpha-actinin antibody levels were higher in patients with renal flares (p = 0.02) and correlated independently with anti-dsDNA antibody levels by enzyme-linked immunosorbent assay (p < 0.007) but not with other disease features. In the random ANA group, 14 individuals had anti-alpha-actinin antibodies. Of these, 36% had SLE, while 64% suffered from other, mostly autoimmune, disorders. Antibodies binding to alpha-actinin were detected in 20% of SLE patients but were not specific for SLE. They correlate with anti-dsDNA antibody levels, implying in vitro cross-reactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE.

Actinin↗

PubMed1997

Fc gamma RIIa polymorphism in systemic lupus erythematosus.

OBJECTIVES: Polymorphism of the phagocyte IgG receptor Fc gamma RIIa may modulate immune complex mediated inflammation, particularly when immune complexes contain IgG2. Previous studies suggest that this polymorphism may be an important risk factor for lupus nephritis. Fc gamma RIIa is biallelic, the alleles R and H each having a gene frequency of about 50%. Nephritis has been associated with an increased frequency of the R allele. The frequency of common Fc gamma RIIa alleles was examined in white subjects from the United Kingdom and Greek subjects with systemic lupus erythematosus (SLE) and healthy controls. METHODS: Fc gamma RIIa genotyping was performed using a single step polymerase chain reaction technique, which differentiates the two major alleles, R and H. Two study populations were examined: (a) white subjects from the United Kingdom: 66 controls and 81 with SLE (19 of whom had renal disease) and (b) Greek: 52 controls and 42 with SLE (19 with renal disease). RESULTS: No significant relation was observed between Fc gamma RIIa genotype and susceptibility to SLE or SLE nephritis. CONCLUSIONS: The Fc gamma RIIa R allele does not seem to be associated with SLE (with or without renal disease) in our United Kingdom white or Greek populations.

Alleles↗

PubMed2001

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.

Administration, Oral↗

PubMed2002

Antiphospholipid syndrome nephropathy in systemic lupus erythematosus.

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.

Adolescent↗

PubMedDate not supplied

Lupus erythematosus: systemic and cutaneous manifestations.

Skin and joint involvements are the most commonly occurring manifestations of systemic lupus erythematosus. There are 3 forms of cutaneous lupus: chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. Joint manifestations are usually not associated with warmth of the joints and may be only associated with pain and swelling. Painful or swollen joints respond rapidly to small or moderate doses of corticosteroids, whereas cutaneous manifestations usually respond to antimalarial drugs. Anti-Ro is associated closely with a photosensitive rash and with subacute lupus.

Cardiovascular System↗

PubMed1995

Association of systemic lupus erythematosus and gluten enteropathy.

Systemic lupus erythematosus presents various clinical manifestations. The coexistence of systemic lupus erythematosus and celiac sprue has been rarely reported. We present a patient who had systemic lupus erythematosus with malabsorption demonstrating characteristic clinical and pathologic findings of celiac sprue (gluten enteropathy).

Celiac Disease↗

PubMed1987

Abnormal responses to ingested substances in murine systemic lupus erythematosus: apparent effect of a casein-free diet on the development of systemic lupus erythematosus in NZB/W mice.

To assess the development of oral tolerance to casein in NZB/W female mice, they must be bred and raised on a casein free diet. We examined the specific immune responses of the mice to the long term experimental feeding of casein. Twelve of fifteen casein free mice were still alive at 10 months of age, although by this age only 1/10 mice eating the normal diet was still alive. The casein free mice had markedly less anti-DNA antibody, their IgM to IgG antinative DNA switch was delayed and deposits of immunoreactants in the glomeruli were greatly decreased. The reason for this apparent effect of the removal of casein from the diet is unknown; however, immunostimulatory and endorphin-like regions have recently been reported in casein.

Animals↗

PubMed1998

Long-term outcome of kidney transplantation in patients with systemic lupus erythematosus: a multicenter study. Groupe Cooperatif de Transplantation d'île de France.

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.

Adult↗