High-dose Intravenous Cyclophosphamide Research Articles

#468 Voclosporin-based, triple-immunosuppressive therapy vs high-dose glucocorticoid-based dual-immunotherapy for lupus nephritis: a propensity analysis

Abstract Background and Aims Voclosporin is a second generation calcineurin inhibitor (CNI) approved for the treatment of adults with active lupus nephritis (LN) in combination with immunosuppressive therapy. An integrated analysis of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies concluded that combining voclosporin with lower-dose mycophenolate mofetil (MMF, 2 g/day) and low-dose glucocorticoids (GCs) led to significantly greater and earlier reductions in proteinuria when compared to MMF and GCs alone. This is an important finding as early reduction in proteinuria is associated with improved long-term kidney survival and mortality. Yet, dual-immunosuppressive regimens consisting of high-dose glucocorticoids and either intravenous cyclophosphamide (IVC) or higher doses of MMF (>2 g/day) continue to be frequently used for the initial management of active LN despite their association with incomplete efficacy and dose-dependent toxicities. Method All three studies enrolled participants with active LN. In AURA-LV and AURORA 1, participants received voclosporin 23.7 mg BID in combination with MMF (target 2 g/day) and oral GCs (25 mg/day tapered to 2.5 mg/day by Week 16). In ALMS, MMF (target 3 g/day) or IVC (0.5 to 1.0 g/m2/month × 6) was added to oral GCs initiated at a maximum dose of 60 mg/day, tapered every 2 weeks to 10 mg/day. Propensity score methodology was used to generate groups of matched participants (ALMS [MMF and IVC] vs. AURA-LV/AURORA 1 [voclosporin]) based on demographic and disease characteristics. Safety and efficacy were assessed at 3 and 6 months. Results Propensity matching identified 179 pairs of participants with similar demographics and baseline disease characteristics. Mean cumulative exposure to GCs was more than 2-fold higher in the IVC and MMF cohorts of ALMS than AURA-LV/AURORA 1 participants over both 3 and 6 months. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS, although more participants in AURA-LV and AURORA 1 reported hypertension and anemia (Table 1). Due to the known hemodynamic effects of calcineurin inhibition, there was a small decrease in mean eGFR in the AURA-LV/AURORA 1 participants in the first few weeks of treatment after which mean eGFR remained stable; AURA-LV/AURORA 1 participants also had an increased rate of events of GFR decreased. The incidence of serious AEs was similar across treatments. In the first 3 months of treatment, significantly more AURA-LV/AURORA 1 participants achieved a reduction in UPCR >25% from baseline (91.6% vs 69.3%; odds ratio [OR] 4.75, 95% confidence interval [CI] 2.56, 8.84; p < 0.0001). Over six months of treatment, mean (SD) change from baseline in UPCR was −3.1 (2.9) g/g in voclosporin-treated patients in AURA-LV and AURORA 1 compared to −2.4 (3.3) g/g in IVC- or MMF-treated participants in ALMS (Fig. 1). Conclusion Voclosporin-based, triple immunosuppressive therapy was associated with an improved safety profile as well as greater and earlier reductions in proteinuria compared to more conventional dual immunosuppressive regimens. These data support treatment guidelines for active LN that recommend both minimizing patient exposure to GCs and use of a multi-targeted treatment regimen as initial therapy.

Long-Term Prognosis of Antimelanoma Differentiation-Associated Gene 5-Positive Dermatomyositis With Interstitial Lung Disease.

Antimelanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis with interstitial lung disease (DM-ILD) progresses rapidly and has a poor prognosis. Previously, we reported the efficacy of a combination therapy comprising high-dose glucocorticoids (GCs), calcineurin inhibitors (CNIs), and intravenous cyclophosphamide (IV CYC) in a multicenter clinical trial (UMIN000014344). In the present study, we evaluated the long-term outcomes and effects of induction therapy on the maintenance of remission. All participants from our previous trial were followed up for > 5 years. Seventy-three other patients with anti-MDA5-positive DM-ILD from our institute were retrospectively integrated into the previous trial for further analysis. Sixty-eight patients achieved remission and survived for > 6 months. Based on the induction treatment, we classified the patients into 2 groups: (1) group T (n = 56), with triple combination therapy (GCs, CNIs, and IV CYC), and (2) group C (n = 12), with monotherapy/dual therapy. The recurrence-free and drug-withdrawal rates of immunosuppressive agents were compared. The overall survival and recurrence-free survival rates at 5 years were 100% for the participants in the previous trial. The 5-year cumulative withdrawal rates for CNIs and GCs were 70% and 53%, respectively. In a comprehensive analysis, the recurrence-free rates in group T were higher than those in group C (90% vs 56%; P < 0.05). The drug-withdrawal rates of CNIs and GCs at 10 years in group T were also higher than those in group C (79% vs 0% and 43% vs 0%, respectively; P < 0.05). Triple combination therapy in the induction phase can reduce the risk of recurrence and facilitate drug withdrawal in anti-MDA5-positive DM-ILD.

Mass-like Lesions Causing Compression of Large Vessels in Granulomatosis with Polyangiitis: A Case Report.

A 69-year-old woman with a history of otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitis who had been receiving corticosteroid monotherapy presented with shortness of breath. The otitis media had been alleviated, but she had saddle nose. Chest enhanced computed tomography (CT) showed stenoses of the bronchi and large vessels surrounded by mass-like lesions in the mediastinum. These manifestations indicated an active state of granulomatosis with polyangiitis (GPA). After she was started on high-dose corticosteroids and intravenous cyclophosphamide, the mass-like lesions disappeared with improvements of the stenoses. Ameliorating mass-like lesions resulting from GPA requires therapeutic intervention using corticosteroids and immunosuppressants.

Clinical Image: Antineutrophil cytoplasmic antibody-associated vasculitis causing compressive cervicothoracic myelopathy.

The patient, a 64-year-old man, presented with a 6-week history of upper back pain and progressive lower-limb weakness and paraesthesia. Of particular note, he had a past history of chronic sinusitis and otitis media. Examination revealed a spastic paraparesis with sustained clonus, hyperreflexia, and medical research council grade 3/5 weakness in both lower limbs. Magnetic resonance imaging of his cervicothoracic spine revealed a circumferential mass–like lesion extending from C5 to T9 with compression of the spinal cord at T2-T3 (see image). Antineutrophil cytoplasmic antibody (ANCA) testing revealed a perinuclear pattern with a strongly positive myeloperoxidase antibody. Histologic examination demonstrated a dense lymphocytic infiltrate with fibrinoid necrosis of the blood vessel wall consistent with vasculitis. A diagnosis of ANCA-associated vasculitis causing compressive myelopathy was made. Treatment with high-dose glucocorticoids and pulsed intravenous cyclophosphamide was initiated, with almost immediate improvement seen in the patient's neurological status. This highlights the importance of including ANCA-associated vasculitis within the differential causes of spinal lesions. Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection.

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1-3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203-89 605) ng/mL at diagnosis, 48 189.4 (15 537-83 375) ng/mL before IVCY therapy, and 10 721.2 (5637-13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896-45 626) ng/mL, and to 37 464.2 (19 872-58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3-12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.

Comparison of short interval and low dose (SILD) with high dose of cyclophosphamide in the susceptibility to infection in SLE: a multicentrereal-world study

ObjectiveInfection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide...

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study

ObjectivesTo investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA).MethodsThe clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n = 7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n = 13). The primary endpoints were the MPZ retention rate and the IVCY completion rate. The secondary endpoints were adverse events and changes in the Birmingham Vasculitis Activity Score (BVAS), Vascular Damage Index (VDI), eosinophil counts, and concomitant CS doses, and the extent and rates of these changes were compared between the MPZ and IVCY groups.ResultsRegarding the primary endpoints, the MPZ retention rate was 100%, and the IVCY completion rate was 61.5%. Regarding the secondary endpoints, adverse events were detected in 2/7 patients (28.6%) in the MPZ group and 7/13 patients (53.8%) in the IVCY group. BVAS and eosinophil counts significantly decreased in both groups at and after month 1, but there was no significant difference in the magnitude of changes between the two groups. VDI scores did not significantly increase in either group, and the degree of changes did not significantly differ between the two groups. Although concomitant CS doses significantly decreased at and after month 1 in both groups, the rates of decrease in CS doses at and after month 3 were significantly higher in the MPZ group.ConclusionsThis study suggested that the use of MPZ as remission induction therapy for severe EGPA might be safe and effective for controlling disease activity and reducing CS doses.

Tofacitinib in interstitial lung disease complicated with anti-MDA5 antibody-positive dermatomyositis: A literature review.

Interstitial lung disease (ILD) associated with idiopathic inflammatory myopathy is a life-threatening organ involvement [1–4]. Particularly, anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with rapid progressive and refractory ILD [1,2], and the prognosis of patients with anti-MDA5-positive ILD is extremely poor, with the mortality of 31.7–45.0% [2,5]. Thus, establishment of optimal treatment strategy is an urgent task. Recently, the effectiveness of combined immunosuppressive regimen consisting of high-dose glucocorticoids, calcineurin inhibitors, and intravenous cyclophosphamide treatment [6], rituximab [7,8] and plasma exchange [9] have been reported, however, many patients have still failed to respond to those treatment resulting in a fatal consequence. Tofacitinib is a Janus kinase (JAK) inhibitor approved for rheumatoid arthritis, ulcerative colitis, and atopic dermatitis. It inhibits JAK1, JAK3, and, a lesser extent, JAK2 [10]. Tofacitinib has been...

Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis.

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is a rare autoimmune disease predominantly reported in East Asia. MDA5+ DM is an intractable disease with impressively high mortality due to rapid-progressive interstitial lung disease (RPILD). Other typical clinical manifestations comprise DM-specific rash (Gottron's papules, heliotrope rash) and amyopathic/hypomyopathic muscle involvement. Multiple prognostic factors have been identified. Baseline forced vital capacity (FVC) %-based staging could serve as a simplified risk stratification system. Serum biomarkers including MDA5 Ab titers, ferritin, KL-6 levels, and CD4+CXCR4+ T cell percentage could provide additional surrogate value of ILD severity and treatment response, as well as potential predictive value for survival. Spontaneous pneumomediastinum (PNM), ground-glass opacity (GGO), and consolidation were demonstrated to be the most significant features in pulmonary high-resolution computed tomography (HRCT) findings of MDA5+ DM-ILD. The semi-quantitative assessment of lesions in HRCT has also been demonstrated relevant to the outcome. The current treatment of this disease is still largely empirical. Immunosuppressive treatments, i.e., "triple therapy" (combination of high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide) and JAK inhibitor-based therapy, are the mainstream regimens for MDA5+ DM-ILD, supported by the recently published trials. However, more efficacious regimen with favorable safety profile and high-level evidence is still urgently demanded for patients with MDA5+ DM-ILD, especially those at advanced-stage. We will summarize the terminology, etiology and pathogenesis, clinical features and outcome, prognostic factors, and treatment of MDA5+ DM-ILD in this review.

A rare case of cutaneous vasculitis with diagnostic difficulty in coexistence of serum anti‐PR3 antibody and in vivo IgA deposits in the skin

Dear Editor, Granulomatosis with polyangiitis (GPA) represents a necrotizing granulomatous inflammation involving the upper and lower respiratory tract with necrotizing vasculitis at small- to medium-sized vessels.1 GPA is also characterized by the presence of serum antineutrophil cytoplasmic antibodies (ANCAs), consisting of ANCA-associated vasculitis (AAV). In contrast, IgA vasculitis is an immune complex disease affecting small vessels in various organs, involving the skin, gastrointestinal tract, kidneys, and arthritic joints.1 Both disease phenotypes sometimes overlap and are difficult to discriminate. Here, we report an exemplified case of cutaneous vasculitis with simultaneous positivity for in vivo IgA immunofluorescence in the dermal small vessels and serum antiproteinase 3 (PR3) ANCA. An otherwise healthy 40-year-old Japanese man presented with high-grade fever, arthralgia, and painful swelling with purpura in bilateral lower limbs 2 days ago. Examination showed multiple small-sized palpable purpura and violaceous, coalescent papules (Figure 1A,B). Histopathology of the lesional purpura showed leukocytoclastic vasculitis without granuloma formation throughout the dermis (Figure 1C,D). Direct immunofluorescence showed IgA deposits at blood vessel walls (Figure 1E). Abnormal laboratory data included an elevated serum PR3-ANCA (89.9 U/mL; ref. <3.5 U/mL). Serum cryoglobulins and renal function were within normal limits. Ophthalmologic examination revealed no abnormalities. Contrast-enhanced computed tomography (CT) detected no granulomas or organ involvements, except mild ethmoid sinusitis and pulmonary emphysema. He was initially diagnosed with IgA vasculitis with anti-PR3 ANCA and treated with oral prednisolone 40 mg/d (0.5 mg/kg/d). His fever and arthralgia were subsided, but the purpuric eruption rapidly spread to the trunk. Upon the ongoing oral steroid, a high-dose intravenous cyclophosphamide was added, and the skin lesions improved with concomitant decrease of serum PR3-ANCA titer. Thereafter, the daily dose of oral steroid was tapered to 5 mg/d during 1 year of follow-up, but his symptoms have never relapsed. Our case poses a diagnostic dilemma in the coexistence of in vivo IgA deposit at the dermal blood vessels and seropositive anti-PR3 ANCA. Moreover, the serum antibody titer was consistent with the clinical course, supporting the provisional diagnosis of GPA rather than IgA vasculitis, albeit no detectable granulomas in any organs. An alternative diagnosis arises the possibility of IgA vasculitis with positive PR3-ANCA. However, there has been a documented case who primarily diagnosed with IgA vasculitis but later developed pulmonary hemorrhage with granuloma and required immunosuppressive therapy2. A careful follow-up is hence mandatory for life-threatening complications abruptly activated in GPA. Antineutrophil cytoplasmic antibody-associated vasculitis has been considered as a pauci-immune condition that is unrelated to immune complex basis.3 However, an updated case series implicates the possible overlapping of AAV and immune complex vasculitis, as seen in ANCA-associated glomerulonephritis with complement and/or immunoglobulin deposition in kidney.4, 5 The concept is strengthened by observation that the complement depletion completely blocked anti-MPO ANCA-induced crescentic glomerulonephritis in mice.6 Alternative complement activation may, in part, coexist as the pathogenic modifier of AAV. Combining these with evidence that the tissue-bound complements and immunoglobulins are degraded by locally infiltrating leukocytes,7 the disease stage-/tissue-dependent activation of immune complex system may aid interpretation of the complex pauci-immunity in AAV. The authors declare no conflict of interest. Obtained. Approval of the research protocol: No human participants were included. Registry and the Registration No.: N/A. Animal Studies: N/A.

Treatment of necrobiotic xanthogranuloma - a systematic review.

Necrobiotic xanthogranuloma (NXG) is an uncommon non-Langerhans cell histiocytosis involving skin and extracutaneous tissues. The lesions are usually asymptomatic and commonly appear in the periorbital area. Paraproteinemia is closely associated with NXG and its pathogenesis remains unclear. NXG prognosis is poor with several treatments showing variable results. Treatment of monoclonal gammopathy with alkylating agents does not necessarily influence the activity of the skin disease and vice versa. The aim of this systematic review is to summarize all reported treatments of necrobiotic xanthogranuloma of the skin, with or without underlying malignant condition and based on articles from the PubMed database using the query 'necrobiotic xanthogranuloma treatment', both in English and German, about 'human' subjects and published between 1980 and 2014, documenting adequate treatment for NXG. Mainly individual case reports, small case series and retrospective studies were found. Treatment options include topical and systemic corticosteroids, thalidomide, high-dose intravenous immunoglobulin (IVIG), chlorambucil, cyclophosphamide, fludarabine, rituximab, melphalan, infliximab, interferon alpha, cladribine, hydroxychloroquine, azathioprine, methotrexate, laser therapy, radiotherapy, surgery, PUVA, plasmapheresis and extracorporeal photopheresis. Randomized controlled trials and studies on long-term outcomes after treatment were not found and are necessary to focus on in the future.

Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.

AB0497 The Euro-Lupus Protocol plus Tacrolimus for Lupus Nephritis: Potentiality of Multi-Target Therapy

BackgroundMulti-target therapy using two immunosuppressive drugs with different mechanism of action such as mycophenolate mofetil and tacrolimus (Tac) for lupus nephritis (LN) 1 seems to be a promising treatment strategy....

THU0284 Health-Related Quality of Life in Patients with Proliferative Lupus Nephritis Treated with Short-Term High-Dose Intravenous Cyclophosphamide Followed by Mycophenolate Mofetil

BackgroundFor decades, high-dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded standard therapy for systemic lupus erythematosus (SLE) patients with proliferative lupus nephritis (LN). Previously, we showed that induction...

AB0369 Evaluation of the eurolupus protocol in lupus nephritis treatment in an internal medicine department

BackgroundLupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus since it is the major predictor of poor prognosis. Corticosteroids and immunosuppressive treatment has transformed the...

Anti-MDA5 (melanoma differentiation-associated gene 5) antibody and dermatomyositis with rapidly progressive interstitial pneumonia

Anti-MDA5 antibody is one of the dermatomyositis-specific autoantibodies and anti-MDA5-potsitive patients show characteristic clinical features, such as hypomyositis, high prevalence of acute/subacute interstitial pneumonia (A/SIP) with poor prognosis, hyperferritinemia and elevated hepatobiliary enzyme. We found that serum IL-6, IL-18, M-CSF and IL-10 were significantly higher and serum IL-12 and IL-22 were significantly lower in anti-MDA5-positive patients than in anti-MDA5-negative patients before treatment. Taking together these serological findings, we hypothesized that monocyte and macrophage activation may underlie in the pathophysiology of anti-MDA5-positive patients. They rarely survive after they become to need oxygenation, and so need to be treated as soon as possible once the diagnosis has been made. Intensive regimen of combined immunosuppressive therapy (high-dose corticosteroids, oral cyclosporin and intravenous cyclophosphamide (IVCY, 900-1000 mg/m(2) in every other week)) improved the survival rate of anti-MDA5-positive patients. Especially, the serum ferritin levels tended to go down about 14 days after IVCY, suggesting that IVCY might be a key drug in the treatment of anti-MDA5-positive A/SIP patients.

Successful Treatment of Class IV+V Lupus Nephritis with Combination Therapy of High-dose Corticosteroids, Tacrolimus and Intravenous Cyclophosphamide

A substantial number of patients with lupus nephritis (LN) are refractory to conventional glucocorticoid (GC) treatment. Although many of these patients respond to immunosuppressive drugs such as intravenous cyclophosphamide (IVCY), azathioprine (AZA), mizoribine, tacrolimus, cyclosporine A (CSA) and mycofenolate mofetil (MMF), some remain refractory to such therapies. Recent studies of multi-target therapies have reported effective outcomes for immunosuppression following renal transplantation and refractory LN when therapy consists of two or more immunosuppressive drugs with different mechanisms of action. We herein report a case of LN unresponsive to IVCY that was successfully treated with the addition of tacrolimus and discuss the usefulness of multi-target therapy for LN.

A young woman with systemic lupus erythematosus and extensive mesenteric vasculitis involving small and medium vessels

History of the present illness The patient had 2 recent hospital admissions. Two months prior to her current presentation, she presented to the emergency department with a tooth abscess for which she underwent incision and drainage, and received a 1-week course of penicillin. One week later, she was admitted with a fever of 40.8°C and was noted to have tooth decay on panoramic radiographs without evidence of an abscess. She was treated with intravenous vancomycin and piperacillin tazobactam for 48 hours and then switched to oral clindamycin. Because of her elevated international normalized ratio (INR), she was unable to undergo tooth extraction prior to discharge. Two weeks later, she was readmitted with 4 days of recurrent fevers, malaise, diffuse arthralgias, and increased dyspnea with minimal exertion. Previous lupus exacerbations were characterized by arthralgias, rash, and hemolytic anemia. On this admission, laboratory evaluation revealed leukocytosis, worsening anemia and thrombocytopenia, creatinine of 0.7 mg/dl, alkaline phosphatase of 127 units/liter (normal value 111), spot urine proteinto-creatinine ratio of 1.47 (prior 1.1), low C3 and C4, and an increase in her double-stranded DNA by enzyme immunoassay from 120 to 768 IU/ml (normal value 30). She was empirically treated with vancomycin and piperacillin tazobactam given her recent tooth infection. The elevated alkaline phosphatase level prompted an abdominal ultrasound that showed multiple small hypoechoic areas in the spleen. An extensive infectious evaluation, including blood cultures, fungal serologies, knee arthrocentesis, magnetic resonance imaging of the lumbar spine, transthoracic and transesophageal echocardiograms, and computed tomography of the chest, abdomen, and pelvis, was negative. Her viral serologies were also unremarkable, other than evidence of IgG seropositivity for cytomegalovirus (CMV) with a negative viral load, consistent with prior exposure. Despite broad-spectrum antibiotics, she remained febrile. Her baseline prednisone dose of 12.5 mg was increased to 60 mg daily for possible lupus flare, after which she defervesced within 48 hours. Her thrombocytopenia was thought to be secondary to SLE-related idiopathic thrombocytopenic purpura because it resolved with high-dose steroids and intravenous immunoglobulin. She was discharged home 11 days after admission. The patient remained afebrile for 1 week at home. During this period she developed new-onset progressive upper abdominal pain with meals lasting 20–30 minutes. She denied associated constitutional symptoms, diarrhea, hematochezia, or melena.

Rescue of kidney function in a toddler with anti-GBM nephritis

Anti-glomerular basement membrane (anti-GBM) nephritis is rare in childhood with few published cases. We report a 19-month-old boy with rapidly progressive glomerulonephritis (RPGN) due to anti-GBM nephritis. Treatment was started under 2 weeks after presentation and included plasma exchange, intravenous high-dose methylprednisolone, intravenous cyclophosphamide and mycophenolate as mainstay medication. The treatment was rapidly effective with immediate decrease in anti-GBM titres and plasma creatinine. Three years after presentation, the boy has normal kidney function, blood pressure and no residual disease. The successful outcome was likely due to the rapid recognition of the anti-GBM antibodies as the cause of RPGN and aggressive primary treatment.

Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

ObjectivesThe objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with...