Management of lupus nephritis—current perspectives

Systemic lupus is a complex disease that poses a lot of management challenges. The introduction of the International Society of Nephrology (ISN)/RPS classification, which has attempted to bring about a more standardized approach to reporting of renal biopsy, plays an important role in the management and prognostication in patients with lupus nephritis (LN). The standard of care for severe proliferative LN had been with pulse cyclophosphamide. There is emerging evidence for use of mycophenolate mofetil (MMF) as an alternative therapy for both induction and maintenance therapy, especially in milder forms of disease. Many biological response modifiers are in the pipeline. Rituximab is the most studied one in the setting of refractory LN with conflicting evidence. Azathioprine remains a cheaper alternative to the more powerful, expensive therapies and has a role in maintenance immuno-suppression. The optimal management of membranous lupus remains controversial till date.     

Chilblain lupus erythematosus—a review of literature

Chilblain lupus erythematosus (CHLE) is a rare, chronic form of cutaneous lupus erythematosus. Sporadic cases and two families with autosomal dominant-inherited CHLE have been reported. In familial CHLE, two missense mutations in TREX1 encoding the 3'-5' repair exonuclease 1 were described in affected individuals. The pathogenesis of sporadic CHLE remains unknown. Up to 20% of patients develop systemic lupus erythematosus (SLE). An association with anorexia is discussed. In many cases, there is good response to symptomatic therapy. SLE therapeutics have good effects on SLE-typical symptoms but not on chilblains themselves. This article reviews the clinical presentation, pathogenesis, diagnosis and treatment of CHLE. As an index patient with unique features, we report a 13-year-old boy developing CHLE after anorexia nervosa. Sequencing of TREX1 was normal. With psychotherapeutic support for anorexia and after antibiotic therapy, topical steroids, physical warming and calcium channel blockers, the patient experienced significant relief. Improvement of phalangeal perfusion was demonstrated by angio-MRI.     

An evaluation of leflunomide in the treatment of class Ⅴ lupus nephritis

Objective To investigate the efficacy and safety of leflunomide as induction and mainten-ance therapy for class Ⅴ lupus nephritis. Methods Sixteen patients with lupus nephritis (of which, three proven with Ⅴ +Ⅲ, six with Ⅴ+Ⅳ ), proven by renal biopsies, were included in this study. ALL patients rec-eived LEF plus prednisone treatment. For induction therapy, all patients were given an initial loading dose of LEF 60 mg daily for three days, followed by 20 mg daily for the whole induction treatment period. Prednisone was given starting from 0.8 mg per kilogram daily, then tapered four weeks later. After twenty-four weeks, the dosages of LEF and prednisone were 10 mg/d, 5～10 mg/d respectively during maintenance therapy. We asses-sed total remission rates in the end of twenty-four weeks, as well as the changes of system lupus erythematosus disease activity index (SLEDAI), urinary protein per twenty-four hours (24 h Upr), serum albumin, serum creatinine level, complement C3, complement C4, C reactive protein, serum titer of ANA and anti-dsDNA be-fore treatment, 12 weeks, 24 weeks and 48 weeks after treatment respectively. Meanwhile, seven patients received repeated renal biopsies after completing induction therapy, so we compared pathological activity index (AI) and chroniciry index (CI) between pre-therapy and post-therapy at the same time. T and t' test were selected. Results Sixteen patients were followed-up. After 24 weeks induction therapy, the total remission rate was 75.0%; SLEDAI was significantly lower than pre-therapy [(15.4±3.5) vs (6.9±1.7), P<0.05]; 24 h Upr was also significantly lower than pre-therapy [(5.8±2.2) g vs (l.3±0.5) g, P<0.01 ]. Unfortunately, all seven patients performed repeated renal biopsies with class Ⅴ lupus nephritis again histologically, of which two were transformed other cater-ofies. Comparing with that of pre-therapy, AI was improved after therapy [(2.4±0.9) vs (1.7±0.8), P<0.05]. However, CI indicated no difference. Adverse events including major infection occurred in four patients. The adverse events happened at the 12 th week after treatment. Conclusion The efficacy of LEF plus corticoster-oids as induction and maintenance therapy for class Ⅴ lupus nephritis is remarkable and the tolerance of patients is good.     

High risk of tuberculosis in systemic lupus erythematosus?

The incidence and severity of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) varies greatly among different series. In addition, prospective data are scarce. The aim of this study is to analyse the frequency and severity of TB in our cohort of lupus patients. We analysed data from a prospective database of a single center cohort of 232 patients with SLE (ACR criteria). Prophylaxis with isoniazid was not regularly administered. We identified all cases of TB diagnosed during 10 years (January 1994 to December 2003). The following variables were analysed: annual incidence of TB, location of infection and response to therapy. Data from published series reporting on the incidence of TB among SLE patients were extracted. Three patients (1.3%) suffered clinically manifest TB in 1603 patient-years of follow-up, resulting in an incidence of 187 cases/100,000 patient-years (95% CI 39-547). The pooled annual incidence of TB infection in our area during this period was 30/100,000 individuals. We recorded two cases of pulmonary TB and one case of tuberculous pleurisy. All patients had good response to therapy. The annual incidence of TB among SLE patients in other series, most of them from developing countries, varied between 150/100,000 patients in Turkey and 2450/100,000 patients in India. Of note, high prevalence of extrapulmonary forms as well as elevated TB-associated mortality was reported in most series. TB was more frequent in SLE patients than expected in the general population. We did not see any cases of disseminated infection and all patients had good response to treatment. Our data compare favourably in terms of incidence, severity and outcome with those from highly endemic areas.     

An evaluation of leflunomide in the treatment of class Ⅴ lupus nephritis

Objective To investigate the efficacy and safety of leflunomide as induction and mainten-ance therapy for class Ⅴ lupus nephritis. Methods Sixteen patients with lupus nephritis (of which, three proven with Ⅴ +Ⅲ, six with Ⅴ+Ⅳ ), proven by renal biopsies, were included in this study. ALL patients rec-eived LEF plus prednisone treatment. For induction therapy, all patients were given an initial loading dose of LEF 60 mg daily for three days, followed by 20 mg daily for the whole induction treatment period. Prednisone was given starting from 0.8 mg per kilogram daily, then tapered four weeks later. After twenty-four weeks, the dosages of LEF and prednisone were 10 mg/d, 5～10 mg/d respectively during maintenance therapy. We asses-sed total remission rates in the end of twenty-four weeks, as well as the changes of system lupus erythematosus disease activity index (SLEDAI), urinary protein per twenty-four hours (24 h Upr), serum albumin, serum creatinine level, complement C3, complement C4, C reactive protein, serum titer of ANA and anti-dsDNA be-fore treatment, 12 weeks, 24 weeks and 48 weeks after treatment respectively. Meanwhile, seven patients received repeated renal biopsies after completing induction therapy, so we compared pathological activity index (AI) and chroniciry index (CI) between pre-therapy and post-therapy at the same time. T and t' test were selected. Results Sixteen patients were followed-up. After 24 weeks induction therapy, the total remission rate was 75.0%; SLEDAI was significantly lower than pre-therapy [(15.4±3.5) vs (6.9±1.7), P<0.05]; 24 h Upr was also significantly lower than pre-therapy [(5.8±2.2) g vs (l.3±0.5) g, P<0.01 ]. Unfortunately, all seven patients performed repeated renal biopsies with class Ⅴ lupus nephritis again histologically, of which two were transformed other cater-ofies. Comparing with that of pre-therapy, AI was improved after therapy [(2.4±0.9) vs (1.7±0.8), P<0.05]. However, CI indicated no difference. Adverse events including major infection occurred in four patients. The adverse events happened at the 12 th week after treatment. Conclusion The efficacy of LEF plus corticoster-oids as induction and maintenance therapy for class Ⅴ lupus nephritis is remarkable and the tolerance of patients is good.     

Do flares of systemic lupus erythematosus decline after menopause?

OBJECTIVE: To study whether flares of SLE decline after menopause. METHOD: 34 postmenopausal SLE patients with premenopausal disease onset were studied. The frequency and severity of flares before and after menopause was compared. 17 postmenopausal onset SLE patients were also included for comparison. RESULT: Flares in postmenopausal SLE patients decreased significantly after menopause (total No. of flares/patient-year before and after menopause were 0.50+/-0.10 and 0.14+/-0.05, respectively, p = 0.002). The frequency and proportion of severe flares also dropped significantly. The rate and magnitude of postmenopausal flares in these patients were similar to those of the postmenopausal onset SLE patients, a subset known to run a more benign course. CONCLUSIONS: SLE flares less frequently and seriously after menopause. While this may suggest a protective role of hypoestrogenemia against lupus flares, the contribution of other factors like disease duration and effective treatment to this postmenopausal decline of flares cannot be separated from menopause per se. Further studies are needed.     

Mycophenylate mofetil: what role in the treatment of lupus?

Improved patient survival following lupus nephritis with the institution of corticosteroids, immunosuppressants and renal replacement therapy allows greater emphasis on long-term management issues. In particular, the recent focus has been on therapies to treat nephritis with fewer adverse effects of cyclophosphamide-including immunosuppressive regimens. Mycophenolate mofetil (MMF) has been used in the field of transplantation for more than 10 years. Following initial anecdotal reports describing benefits of MMF in the treatment of lupus nephritis, randomized, controlled trials have established a role for MMF in the treatment of lupus nephritis. MMF use to treat other lupus manifestations has been evaluated only in anecdotal case reports or series with few well-designed trials. Issues complicating clinical trial design in lupus including appropriate use and interpretation of activity and damage indices, comparable remission and response criteria and stratification of high risk populations have been the subject of much discussion and emerging consensus. As long-term outcomes in lupus improve, the toxicity of therapy and risk of relapse become increasingly important determinants of choice of therapeutic agents.     

Rowell’s syndrome: presenting features of systemic lupus erythematosus

A subset of patients with lupus erythematosus develops erythema multiforme-like skin lesions with speckled pattern of antinuclear antibodies, positive rheumatoid factor, anti-Ro (SS-A), and anti-La antibodies (SS-B), which known as Rowell’s syndrome. We report an adolescent boy presented with erythema multiforme-like skin lesions and pericardial effusion; he fulfilled criteria of both Rowell’s syndrome and systemic lupus erythematosus (SLE). Such initial presentation of SLE is rarely reported in literature.     

Can systemic lupus erythematosus be the cause of collapsing glomerulopathy?

Collapsing glomerulopathy is a severe form of glomerular injury, closely associated with HIV infection, characterized by the collapsing feature of glomerular damage with frequent tubulointerstitial involvement and rapid progression to terminal renal failure. The etiopathogenesis in non-HIV infected patients remains obscure. We reported a patient whose diagnosis of collapsing glomerulopathy (CG) and systemic lupus erythematosus (SLE) was done simultaneously and described the diseases characteristics suggesting that SLE could be an etiologic factor for the induction of this glomerulopathy, clinical evolution and treatment.     

Skin lesions--an indicator of disease activity in systemic lupus erythematosus?

Cutaneous manifestations have great diagnostic value for systemic lupus erythematosus (SLE). In this study we tried to establish a correlation between lupus erythematosus LE-specific and LE-nonspecific cutaneous lesions and disease activity measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sixty-six patients with SLE were evaluated. They were divided into three groups having: (1) only LE-specific lesions (38 or 58.46%); (2) only LE-nonspecific lesions (4 or 6.15%); and (3) both types of lesions (23 or 35.38%). Results were analyzed using the Student t-test. Patients with LE-nonspecific skin manifestations had significantly increased disease activity compared to those with only LE-specific lesions. The number of different skin lesion types also correlated with disease activity. It was significantly increased in a group with three different types of lesion, either specific or nonspecific. Patients with only one type of lesion had mild disease. An intermediate disease activity was found in the group with two different lesion types. Lupus-specific skin manifestations serve primarily as an important diagnostic clue. In conclusion, patients with LE-nonspecific lesions have significantly more active SLE than those with LE-specific lesions and may therefore require more intensive therapy and disease monitoring.     

Lack of association of Fc��RIIIb polymorphisms with systemic lupus erythematosus: a meta-analysis

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Fcγ receptor genes have been suggested to play an important role in the pathogenesis of SLE and lupus nephritis (LN). This study aims to assess the association between FcγRIIIb-NA1/NA2 polymorphism and the susceptibility to SLE and lupus nephritis. Relevant studies were identified from electronic databases. A meta-analysis was performed for heterogeneity test and pooled OR calculation. The overall OR of NA2/NA2 homozygous genotype and NA2 allele frequency showed no significant association with SLE and lupus nephritis. Similarly, the association between FcγRIIIb-NA1/NA2 polymorphism and SLE and lupus nephritis was not found in European and Asian population. Taken together, our results suggest that FcγRIIIb might not be a susceptibility gene for SLE and lupus nephritis.     

Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature

Clinical Rheumatology - The induction of autoantibodies is common following therapy with anti-TNF-α agents. However, anti-TNF-α-induced lupus (ATIL) is rare. We assessed the clinical...     

Generalized megaviscera of lupus： Refractory intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus

Dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus （SLE）. Chronic intestinal pseudoobstruction （CIPO） resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation （megacholedochus）. While the molecular pathogenesis is largely unknown, observed histopathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis. High dose immunosuppression usually results in resolution of symptoms with recovery of smooth muscle function, indicative of an autoimmune etiology. We report a patient with SLE who presented with intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus, and present images that illustrate megaviscera simultaneously involving all 3 visceral organs. Since the co-manifestation of all 3 is unusual and has been reported only once previously, we have termed this rare clinical syndrome generalized megaviscera of lupus （GML）. Although the SLE disease-activity parameters responded to aggressive immunomodulative therapy in our patient, clinical evidence of peristaltic dysfunction persisted in all involved viscera. This is a variation from the favorable outcomes reported previously in SLE patients with GML and we attribute this poor clinical outcome to disease severity and, most importantly, delayed clinical presentation. Since inflammation followed by atrophy and fibrosis are key aspects in the pathogenesis and natural history of GML, the poor response in our patient who presented late in the clinical course may be the result of ＇burnt out＇ inflammation with irreversible end-stage fibrosis. Thus, early recognition and timely initiation of treatment may be the key to recover visceral peristaltic function in patients with GML.