Dengue fever evolving into systemic lupus erythematosus and lupus nephritis: a case report

Dengue viremia may be the trigger for immune complex formation in patients who are predisposed to developing autoimmune disease. We report a rare case of dengue virus infection evolving into systemic lupus erythematosus (SLE) and lupus nephritis. To the best of our knowledge this is the first case of dengue fever evolving into lupus nephritis. A 22 year old female presented with having had high grade fever, skin rash, breathlessness, retro-orbital pain, abdominal pain, arthralgias and myalgias for 10 days. She tested positive for dengue immunoglobulin M (IgM). She was given supportive treatment and was subsequently discharged. Four weeks later she developed recurrent fever, arthralgia, rash and anasarca. She was suspected as having SLE with active lupus nephritis. Antinuclear antibody (ANA), and anti double stranded deoxyribonucleic acid (anti dsDNA) titers were positive and complements were low. Renal biopsy showed diffuse proliferative glomerulonephritis grade IV. She was treated with steroids and immunosuppressants to which she responded. Dengue viremia incites antibody production, which if excessive causes deposition of viral antigen-antibody immune complexes. This could possibly lead to renal tubular damage and glomerulonephritis in susceptible individuals. Dengue fever leading to development of glomerulonephritis is rarely seen. Our patient developed dengue fever and after a month presented with manifestations of SLE and lupus nephritis. Both dengue fever and SLE have common manifestations of fever, arthralgia, rash, leucopenia with thrombocytopenia and serositis. Bacterial and viral infections may act as a 'trigger' for starting or relapsing lupus activity in genetically predetermined individuals. In our case it may be possible that dengue virus could have triggered a dysfunctional immune response, resulting in the developing of autoimmunity and SLE with lupus nephritis.     

Remission of refractory lupus nephritis with a protocol including rituximab

Immunosuppression with corticosteroids and cyclophosphamide is the standard of care for lupus nephritis. We report a 19-year old woman with lupus nephritis and nephrotic syndrome who had not achieved complete remission after treatment with 15.7 g cyclophosphamide and 13.7 g prednisone. We planned a consolidation phase with: 1) cyclophosphamide 20 mg/kg i.v. every 28 days for three cycles; 2) anti-CD20 chimeric monoclonal antibody (rituximab) 375 mg/m2 i.v. weekly for four weeks; and 3) slow tapering of prednisone p.o., q.o.d., after a reinduction dose during rituximab administration. At the end of this phase the patient achieved complete remission. An indefinite maintenance treatment with methotrexate, cyclosporin and low-dose prednisone was then started. Twenty-four months later the patient remains in remission. In the immunosuppressive treatment of lupus nephritis the insertion of a consolidation phase with rituximab combined with cyclophosphamide achieves a therapeutically important and lasting deletion of the lymphocyte clone responsible for autoimmunity.     

利妥昔单抗治疗系统性红斑狼疮出现血栓栓塞并文献复习

目的与利妥昔单抗相关血栓的不良反应非常罕见,通过学习1例使用利妥昔单抗后出现严重血栓事件患者的临床特点,进一步了解利妥昔单抗的不良反应。方法详细报道1例系统性红斑狼疮(systemic lupus erythematosus,SLE)合并抗磷脂抗体综合征(anti phospholipid syndrome,APS)患者使用利妥昔单抗后出现血栓的临床表现。结果该患者在使用利妥昔单抗治疗3个月后,PLT正常,狼疮不活动,但出现下肢深静脉血栓和肺栓塞。结论利妥昔单抗治疗SLE有效,但给予SLE合并APS患者使用时要警惕血栓形成的风险。     

Acute pancreatitis: an initial presentation of systemic lupus erythematosus

Acute pancreatitis is a rare, but fatal, manifestation of systemic lupus erythematosus. Only 10 systemic lupus erythematosus-associated pancreatitis cases were found in a search of published articles. We report a 24-year-old woman without significant medical history, who was admitted with abdominal pain, nausea and vomiting, which was diagnosed as pancreatitis. It was discovered to be the initial presentation of systemic lupus erythematosus. The first time she was admitted, she recovered with conservative management and steroid therapy. Two months later, she was readmitted to our hospital with symptoms and signs of acute abdomen, which was attributed to her discontinuation of the therapeutic regimen with corticosteroids just after her previous discharge. She underwent laparotomy twice for signs of peritonitis. Despite administration of a monoclonal antibody, rituximab, she died due to the progression of systemic lupus erythematosus activity.     

Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.     

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.     

Refractory thrombotic thrombocytopenic purpura in a lupus nephritis patient

Thrombotic thrombocytopenic purpura is an uncommon disease and is rare in systemic lupus erythematosus. Rarely, patients do not respond to plasma exchange therapy, and treatment options are limited and often disappointing, thus it is a therapeutic challenge to clinicians. We report a patient with lupus nephritis who developed refractory thrombotic thrombocytopenic purpura and was subsequently treated with cyclosporin A. An immediate and sustained response was demonstrated, and she remained well; eventually she was able to be cyclosporin free after the acute episode. Cyclosporin A can be a safe and effective therapeutic option in patients with refractory thrombotic thrombocytopenic purpura.     

Posterior reversible encephalopathy syndrome--an underrecognized manifestation of systemic lupus erythematosus

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is a rare, recently described neurologic condition identifiable by clinical presentation and magnetic resonance image (MRI) appearance. It is associated with renal insufficiency, hypertension, and rheumatologic diseases. Patients present with headache, seizures, loss of vision and altered mental function, and a pattern on imaging studies of predominantly transient, posterior cerebral hyperintensities on T2-weighted MRI. There is a high likelihood of presentation of this syndrome to a rheumatologist. METHODS: Three recent cases of systemic lupus erythematosus (SLE) with PRES, along with 9 previously reported cases, are reviewed. RESULTS: All 3 patients presented with seizures and subacute visual changes in association with lupus nephritis. The first presented with hypertension, complete visual field loss, and status epilepticus 2 weeks after starting oral cyclosporine therapy for refractory lupus nephritis. The second patient was normotensive and presented with seizures and visual symptoms while in hospital with SLE-related pancreatitis and nephritis. The third patient had headache and seizures with severe lupus disease activity including nephritis, pancytopenia, and pulmonary hemorrhage. Cranial MRI showed predominantly posterior signal abnormalities on T2-weighted images, which resolved after cessation of cyclosporine in the first case, treatment with IV cyclophosphamide in the second case, and treatment with cyclophosphamide and plasmapheresis in the final case. Literature review showed that PRES is a manifestation of SLE or a consequence of therapy with calcineurin inhibitors or rituximab. The hallmark features are visual loss and seizures. Severe hypertension (> 170/110 mm Hg) and renal failure were present in the majority of previously identified cases of SLE and PRES. Our second case was normotensive but had marked lupus disease activity. PRES can lead to cerebral infarction. CONCLUSION: With increasing availability of MRI, PRES will be identified more frequently. Swift action to identify potential offending agents, controlling hypertension, and treating active disease can lead to reversal of radiologic and neurologic findings.     

小剂量利妥昔单抗治疗系统性红斑狼疮的临床观察

目的 评价小剂量利妥昔单抗治疗系统性红斑狼疮(SLE)的疗效和安全性.方法 对既往激素和多种免疫抑制剂治疗无效或复发的10例SLE患者,予利妥昔单抗100mg,使用4次,同时仅联合使用激素,观察疗效和不良反应.结果 利妥昔单抗对狼疮肾炎、神经精神性狼疮、顽固性血小板减少以及自身免疫性溶血性贫血均显示有良好的疗效,且起效迅速.10例患者中仅1例出现了泌尿系感染,1例在首剂利妥昔单抗治疗1周后猝死,但不能确定死亡原因与利妥昔单抗相关.结论 小剂量利妥昔单抗治疗SLE有良好的疗效和安全性,并且降低了治疗费用.     

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.     

Fatal Pulmonary Arterial Hypertension Complicating Noncirrhotic Portal Fibrosis

A 25-yr-old female with noncirrhotic portal fibrosis underwent a lienorenal shunt for variceal bleed. Ten years after shunt surgery, she presented with progressive breathlessness, and severe pulmonary arterial hypertension was detected, to which she subsequently succumbed. Autopsy revealed classical plexogenic pulmonary arteriopathy.     

Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis

OBJECTIVE: Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B cell-dependent diseases, including systemic lupus erythematosus (SLE). The purpose of this study was to investigate the histopathologic and clinical effects of combination treatment with rituximab and cyclophosphamide (CYC) in patients with CYC-resistant proliferative lupus nephritis. METHODS: Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Renal biopsies were performed before treatment and during followup. SLE activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group index. In 6 of the 7 patients, immunostaining of lymphocyte subpopulations in the renal tissue was performed before treatment and during followup. RESULTS: At 6 months of followup, significant clinical improvement was noted, with a reduction in SLEDAI scores (from a mean of 15 to 3), anti-double-stranded DNA antibody levels (from a mean of 174 IU/ml to 56 IU/ml), and anti-C1q antibody levels (from a mean of 35 units/ml to 22 units/ml). On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted (from 6 to 3). A reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium was noted in 50% of the patients on repeat biopsy. CONCLUSION: At 6 months of followup, all patients had responded both clinically and histopathologically to combination therapy. For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option.     

Successful rituximab-CHOP treatment of systemic lupus erythematosus associated with diffuse large B-cell non-Hodgkin lymphoma

The authors discuss the case of a 76-year-old female patient who has been suffering from subacute cutaneous lupus erythematosus since 1983. In 1999 she was diagnosed with systemic lupus erythematosus (SLE) based on her symptoms of malar rash, polyarthritis, leukopenia, autoimmune hemolytic anemia and positive anti-DNA antibody test. For this she received methylprednisolone and cyclophosphamide. After 3 years of remission, symptoms of cutaneous vasculitis appeared in 2004, which transitionally responded to treatment with azathioprin and methylprednisolone. Her cutaneous symptoms, however, progressed quickly along with generalized lymphadenopathy, splenomegaly and thrombocytopenia. Immunohistological evaluation of the lymph node biopsy showed diffuse large B-cell lymphoma. She developed complete remission after treatment with six-cycle R-CHOP (rituximab, and reduced doses of cyclophosphamide, vincristin, adriablastin, methylprednisolone). SLE became inactive and her symptoms of vasculitis resolved. The authors are bringing attention to one of the possible late complications of systemic lupus, and also underscoring that treatment with rituximab (+CHOP) was beneficial not only for the lymphoma but the SLE as well.     

Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus—A case report

Background

Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus.

Objective

To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy.

Methods

A case report and review of relevant literature is presented.

Results

A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein?s anomaly in the baby.

Conclusion

To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy.     

Reactivation of systemic lupus erythematosus in a dialysis patient after tuberculous peritonitis

The disease activity of patients suffering from lupus nephritis usually becomes quiescent after the onset of end stage renal failure. Reactivation of lupus activity, especially after a long period of dialysis, is uncommon. Factors that might trigger off lupus reactivation after dialysis have not been well defined. We report a case of a 43-year-old Chinese woman on long-term peritoneal dialysis, who developed lupus reactivation with cerebral involvement 2 weeks after she was diagnosed to have tuberculous peritonitis. The close temporal relationship between the tuberculous peritonitis and the lupus reactivation raise the possibility that the tuberculous infection might have triggered off the lupus reactivation.     

Chronic intestinal pseudo-obstruction in systemic lupus erythematosus due to intestinal smooth muscle myopathy

We report the case of a woman with systemic lupus erythematosus initially manifesting with fever, rash and arthritis, and two years later with Class IV lupus nephritis. Following treatment with cyclophosphamide she developed symptoms and signs of chronic intestinal pseudo-obstruction (CIPO) that was initially thought to be due to a neutropenic enterocolitis. However, persistence of symptoms resulted in segmental resection of the ileum which showed widespread myocyte necrosis and active inflammation within the muscularis propria. A subsequent, more extensive ileocolic resection showed severe diffuse atrophy and fibrosis of the muscularis propria throughout the resected bowel. The absence of mesenteric vasculitis and the clinical response of the CIPO to the immunosupressive regimen of prednisolone and cyclosporin A suggest that the bowel muscle coat changes reflect an intestinal myopathy secondary to systemic lupus erythematosus, and may have an auto-immune etiology.     

Therapy of acute pancreatitis in systemic lupus erythematosus with plasmapheresis and corticosteroids

A 24-year-old woman with systemic lupus erythematosus had, after reduction of corticosteroid therapy, a severe relapse of the disease with hepatitis, nephritis and pleurisy. After admission to the hospital, she was given 60-80 mg/day of prednisone and acute pancreatitis developed on the third day. Plasmapheresis, followed by injection of 1 g of methylprednisolone, was started. This combined therapy induced a prompt and complete recovery in a few days.     

Optimum therapeutic approaches for lupus nephritis: what therapy and for whom?

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.     

Recurrent diffuse alveolar haemorrhage in a patient with systemic lupus erythematosus: long-term benefit of rituximab

Diffuse alveolar haemorrhage (DAH) is an uncommon complication of systemic lupus erythematosus (SLE), and recurrences of DAH with remission periods are unusual. We describe a young woman with cachexia as the initial manifestation of SLE who presented posterior reversible encephalopathy syndrome (PRES), intestinal vasculitis and four episodes of DAH even though she was receiving combined immune suppressive therapy. After treatment with rituximab (RTX) the patient has not presented further episodes of DAH.     

Pulmonary haemorrhage and mesenteric vasculitis in a patient with systemic lupus erythematosus

WE Report a 26‐year‐old female patient with systemic lupus erythematosus (SLE) who developed mesenteric vasculitis and pulmonary haemorrhage. This patient initially presented with an acute abdomen and extensive vasculitic rash. While she was being treated for her abdomen she developed fulminant pulmonary haemorrhage requiring mechanical ventilation. With supportive measures and aggressive immunosupression treatment she eventually made a complete recovery.