Bullous systemic lupus erythematosus in a child responding to dapsone. Liu Kwei-Lan,Shen Jui-Lung,Yang Chii-Shuenn,Chen Yi-Ju Pediatric dermatology Bullous systemic lupus erythematosus is a subepidermal blistering disorder that primarily affects young women and only rarely occurs in children. We report a case of bullous systemic lupus erythematosus refractory to corticosteroid therapy in a 12-year-old boy who was successfully treated with oral dapsone. 10.1111/pde.12340
    Refractory Angioedema in a Patient with Systemic Lupus Erythematosus. Habibagahi Zahra,Ruzbeh Jamshid,Yarmohammadi Vahide,Kamali Malihe,Rastegar Mohammad Hassan Iranian journal of medical sciences Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.
    Refractory lupus nephropathy and acquired Factor VIII and IX deficiencies in a patient with systemic lupus erythematosus treated with rituximab. Cui Q-Y,Wu T-Q,Shen H-S,Chen H-F,Yu Z-Q,Wang Z-Y Haemophilia : the official journal of the World Federation of Hemophilia 10.1111/hae.13232
    Short-term add-on tocilizumab and intravenous cyclophosphamide exhibited a remission-inducing effect in a patient with systemic lupus erythematosus with refractory multiorgan involvements including massive pericarditis and glomerulonephritis. Iwai Atsuko,Naniwa Taio,Tamechika Shinya,Maeda Shinji Modern rheumatology We report on a 41-year-old woman with refractory systemic lupus erythematosus with massive pericarditis, macrophage activation syndrome, and glomerulonephritis despite high-dose glucocorticoids and tacrolimus. Tocilizumab dramatically improved pericarditis, and glomerulonephritis was controlled after adding cyclophosphamide. We had to halt tocilizumab and cyclophosphamide due to possible pneumocystis infection after five and three infusions of tocilizumab and intravenous cyclophosphamide, respectively. Nevertheless, no lupus flare had been observed on glucocorticoid monotherapy and enabled further rapid tapering prednisolone. 10.3109/14397595.2014.990409
    Belimumab in refractory organizing pneumonia associated with systemic lupus erythematosus: a case report. Giménez Ai Rebollo,Pastrana D Bellido,Huaranga M A Ramírez,Izquierdo J Ros,Cabrera B,García A Núñez,Rodríguez C C Ramos Lupus Organizing pneumonia is an inflammatory lung entity that presents with a huge variety of clinical, radiological and pathological patterns. Organizing pneumonia can be idiopathic or secondary to other diseases. Corticosteroid therapy is usually the first-line treatment showing clinical improvement in most cases. This report presents the case of a 56-year-old woman with systemic lupus erythematosus who was diagnosed with an organizing pneumonia and showed a poor response to steroid and azathioprine treatment. We considered the use of belimumab, which resulted in excellent clinical and radiological outcomes. 10.1177/0961203319835320
    Lupus protein-losing enteropathy patient with protein C and protein S deficiency-induced thrombosis: A case report with review of the literature. Lertnawapan Ratchaya,Sakonlaya Dussadee Acta reumatologica portuguesa <p>A case report of SLE with PLE in an Asian female; presented with edema, pleural effusion, ascites and profound hypoalbuminemia. She also had severe protein C and protein S depletion from GI loss which caused extensive thrombosis. Her disease was refractory to the treatment with high dose steroid, azathioprine, mycophenolate mofetil and cyclophosphamide. Bowel resection was performed without improvement. Fortunately, the patient responded to another course of pulse methyl prednisolone and a second line medication after surgery.</p>.
    Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency. Van Eyck Lien,De Somer Lien,Pombal Diana,Bornschein Simon,Frans Glynis,Humblet-Baron Stéphanie,Moens Leen,de Zegher Francis,Bossuyt Xavier,Wouters Carine,Liston Adrian Arthritis & rheumatology (Hoboken, N.J.) OBJECTIVE:To identify the underlying genetic defect in a 16-year-old girl with severe early-onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations. METHODS:Whole-exome sequencing and extensive immunologic analysis were performed on samples from the index patient. RESULTS:We identified a de novo p.R779H IFIH1 gain-of-function mutation in a patient with severe early-onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in IFIH1 was recently identified in patients with Aicardi-Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up-regulation of IFIH1 itself. CONCLUSION:This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease). This marked phenotypic heterogeneity, despite an identical mutation, demonstrates the importance of modifying factors in type I IFN-dependent pathologies caused by mutations in IFIH1. 10.1002/art.39110
    Thrombotic microangiopathy in systemic lupus erythematosus: efficacy of eculizumab. El-Husseini Amr,Hannan Schot,Awad Ahmed,Jennings Stuart,Cornea Virgilius,Sawaya B Peter American journal of kidney diseases : the official journal of the National Kidney Foundation Thrombotic microangiopathy (TMA) is a severe disorder with poor outcomes. The cause is unknown for many patients, although TMA is associated with connective tissue disorders, including systemic lupus erythematosus (SLE). While uncommon, TMA is one of the most serious complications of SLE and in many cases may be resistant to therapy. We report a patient with SLE complicated by TMA that was refractory to standard therapy but responded well to eculizumab, with continued remission after 1 year of follow-up. Eculizumab might be useful in the management of resistant cases of TMA caused by SLE. 10.1053/j.ajkd.2014.07.031
    Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin. Brasileiro A,Fonseca Oliveira J,Pinheiro S,Paiva-Lopes M J Lupus The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients. 10.1177/0961203316630116
    Efficacy of Rituximab in a Systemic Lupus Erythematosus Patient Presenting with Diffuse Alveolar Hemorrhage. Montes-Rivera Gabriela,Ríos Grissel,Vilá Luis M Case reports in rheumatology Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus (SLE). Although infrequent, its mortality is very high. While there are no established therapeutic guidelines, DAH has been traditionally managed with high-dose intravenous (IV) corticosteroids, cyclophosphamide, and plasma exchange. The efficacy of alternative therapies such as rituximab has been described only in a few cases. Herein, we report a 25-year-old Hispanic man who presented with acute-onset SLE manifested by polyarthralgia, nephritis, seizures, pancytopenia, severe hypocomplementemia, and elevated anti-dsDNA antibodies. His disease course was complicated by DAH. His condition was refractory to high-dose intravenous (IV) methylprednisolone pulses, IV cyclophosphamide, and plasmapheresis. Given the lack of clinical response, he was started on IV rituximab 375 mg/m weekly for a total of four courses. He rapidly improved after the first two doses. Over the next seven months, he did not present recurrent pulmonary symptoms. Follow-up chest computed tomography did not show residual abnormalities. This case, together with other reports, suggests that rituximab is an effective therapeutic option for DAH in SLE. 10.1155/2017/6031053
    Successful sequential therapy with rituximab and belimumab in patients with active systemic lupus erythematosus: a case series. Gualtierotti Roberta,Borghi Maria Orietta,Gerosa Maria,Schioppo Tommaso,Larghi Paola,Geginat Jens,Meroni Pier Luigi Clinical and experimental rheumatology OBJECTIVES:B cells play an important role in the initiation and progression of systemic lupus erythematosus (SLE). Accordingly, B cell-targeted therapy has been suggested as a new rational approach for treating lupus. Belimumab, a human monoclonal antibody directed against B lymphocyte stimulator (BLyS), was reported as the first biological treatment effective in reducing mild-to-moderate SLE disease activity by using different scoring systems and endpoints. Conversely clinical trials with rituximab, a chimeric monoclonal antibody directed against the CD20 expressed by B cells, have failed to achieve primary endpoints in spite of a number of reports showing its beneficial effects. Anecdotal reports have described the sequential use of rituximab and belimumab as a more effective treatment than using the individual drugs alone, without compromising safety. METHODS:We report a case series of three patients with active SLE refractory to conventional therapies, who underwent treatment with rituximab followed by belimumab as maintenance therapy. RESULTS:We observed a beneficial effect after sequential treatment with rituximab and belimumab. All patients achieved long-standing remission and could reduce or discontinue corticosteroids. Concomitantly, after rituximab administration we observed a rise in BLyS levels, which were dramatically reduced after belimumab introduction. CONCLUSIONS:The modulation of plasma BLyS kinetics in patients undergoing sequential treatment with rituximab and belimumab may represent a possible rationale behind the effectiveness of this combined therapy.
    Secondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: Case series and review of literature. Kello Nina,Khoury Lara El,Marder Galina,Furie Richard,Zapantis Ekaterini,Horowitz Diane Lewis Seminars in arthritis and rheumatism INTRODUCTION:Thrombotic microangiopathy (TMA) is a life-threatening, albeit infrequent, complication of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Recommendations for the treatment of SLE- and APS-related secondary TMA are currently based solely on case reports and expert opinion. Unfortunately, interventions may not yield timely results or effectively halt the progression of TMA. Since complement activation plays a key role in the pathogenesis of secondary TMA due to SLE, APS, a therapy that targets the complement pathway is an attractive intervention. Eculizumab, a recombinant, fully humanized IgG2/IgG4 monoclonal antibody inhibits C5 activation and is FDA-approved for PNH and atypical HUS (aHUS). However, limited case reports are available on its use in treatment of secondary TMA. CASE PRESENTATION AND RESULTS:We present the largest case series to date that includes 9 patients with SLE and/or APS who were successfully treated with eculizumab for refractory secondary TMA. In this case series, we report significant responses in hematology values, renal function and other organs following treatment with eculizumab. At 4 weeks, 75% improvement in platelet counts was observed in 78% of patients. Two-thirds of patients demonstrated >75% improvement of haptoglobin and LDH at four weeks. At 4 weeks, eGFR improved by 25% in half of the patients, and 43% had reductions in proteinuria. Two of 3 patients that required hemodialysis were able to be taken off hemodialysis. CONCLUSION:Based on these observations, we suggest that eculizumab may be a potential treatment option for acutely ill patients with secondary TMA due to SLE and/or APS who have failed standard of care. A collective approach is needed to better elucidate the role and optimal timing of eculizumab use in the management of TMA complicating SLE and/or APS. 10.1016/j.semarthrit.2018.11.005
    Lupus and the Liver: A Case Study. Patel Shaan,Demory Beckler Michelle,Kesselman Marc M Cureus Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of systemic manifestations. Though skin, renal, joint, and hematologic involvement are often associated with SLE, hepatitis is not a common manifestation. While clinically significant hepatopathy in SLE is rare, asymptomatic hypertransaminasemia has been seen in up to 60 percent of SLE patients during the course of their disease and is generally attributed to viral hepatitis, hepatotoxic drugs, or alcohol use. A diagnosis of lupus hepatitis is largely considered a diagnosis of exclusion. There has been a correlation between the presence of ribosomal P autoantibodies with the incidence of lupus hepatitis. Generally, lupus hepatitis responds well to therapy with prednisone, although cases refractory to corticosteroids and conventional immunosuppressants have been described. In these cases, treatment with mycophenolate mofetil has been shown to be effective. Here, we present the case of a 15-year old female who presented with a new diagnosis of SLE with an incidental elevation of her liver function tests (LFTs) and a subsequent finding of hepatomegaly with fatty infiltration. 10.7759/cureus.5477
    Long-term systemic lupus erythematosus disease control after allogeneic bone marrow transplantation. Gladstone D E,Petri M,Bolaños-Meade J,Dezern A E,Jones R J,Fine D,Brodsky R A Lupus Systemic lupus erythematosus (SLE), a disorder of the immune system, is potentially curable by allogeneic bone marrow transplantation (alloBMT). Until recently, alloBMT was limited by donor availability and toxicity. Reduced intensity conditioning (RIC) combined with post-transplantation cyclophosphamide (PTCy) has improved the availability and safety of alloBMT permitting its exploration in severe-refractory autoimmune illnesses. We report the six-year follow-up of a young female whose refractory SLE-associated nephrosis resolved after RIC alloBMT with PTCy. 10.1177/0961203316669242
    Thrombocytopenia resistent to standard therapy in lupus patients - analysis of 3 cases and clinical statement. Pawlak-Bus Katarzyna,Leszczynski Piotr,Kokot Mateusz,Samborski Włodzimierz Annals of agricultural and environmental medicine : AAEM Hematologic disorders, including thrombocytopenia, are a common symptom of systemic lupus - Systemic Lupus Erythematosus (SLE). An important diagnostic and therapeutic issue is the severe and recurrent thrombocytopenia resistant to standard treatment. It requires extensive diagnostics and a multi-directional view on its causes beyond the autoimmune process. Currently, there is no single treatment regimen for these disorders. Corticosteroids (CS) are the first-line drugs, but their chronic use is a big problem, they are not always successful and often generate a number of complications, especially in moderate to high doses. In the case of thrombocytopenia associated with the activity of SLE, immunosuppressive therapy is the gold standard and may result in long-term remission of symptoms and clinical stabilization. The major problem is thrombocytopenia resulting from other causes, such as infection or medications. This study discusses severe recurrent thrombocytopenia on the basis of three clinical cases, analyzing both the various causes of disorders, and providing ways of management and treatment. Special attention is paid to the correlation of thrombocytopenia with the clinical and immunological activity of SLE. It seems that severe and refractory thrombocytopenia may be a critical point and largely determine the management and treatment possibilities of SLE. 10.26444/aaem/80708
    Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience. Olsson Richard F,Hagelberg Stefan,Schiller Bodil,Ringdén Olle,Truedsson Lennart,Åhlin Anders Transplantation BACKGROUND:Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. METHODS:We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. RESULTS:A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. CONCLUSIONS:Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy. 10.1097/TP.0000000000000975
    Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review. de Holanda Maria Izabel,Pôrto Luis Cristóvão,Wagner Teresa,Christiani Luis Fernando,Palma Lilian M P Clinical rheumatology The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse outcome. TMA is described as the association of microangiopathic hemolytic anemia, thrombocytopenia, and an organ injury, frequently the kidney. This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55 days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had rapid improvement in hematological parameters, and dialysis was discontinued 25 days after the first dose. Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS). Twenty patients who received eculizumab with SLE and/or APS have been published to date: 11 were female and mean age at presentation was 31 years. Seven out of the 20 patients presented only SLE, 5 patients only APS and 8 patients both SLE and APS. Eighteen patients underwent plasma exchange, with a mean of 20 (4-120) sessions per patient. Thirteen patients received rituximab. Hematological response was evident in 100% and kidney recovery in 85% of patients. The terminal complement blockade with eculizumab is an optional treatment for patients with SLE and/or APS presenting TMA and refractory to current immunosuppression therapies. Genetic testing may help recognize patients with aHUS and SLE/APS and therefore help to determine length of treatment with eculizumab. 10.1007/s10067-017-3823-2
    Systemic lupus erythematosus exacerbation following cessation of belimumab treatment. Furer V,Zisman D,Pokroy-Shapira E,Molad Y,Elkayam O,Paran D Scandinavian journal of rheumatology OBJECTIVES:Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE. METHOD:Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment. RESULTS:Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and white matter lesions on brain magnetic resonance imaging (MRI), one case of severe pneumonitis and haemolytic anaemia, and one case of a systemic flare, fatigue, arthritis, and severe abdominal pain. CONCLUSIONS:Belimumab therapy has been shown to be beneficial in the management of active SLE, mostly in patients with mucocutaneous and musculoskeletal manifestations. We suggest a possible rebound effect following cessation of belimumab that could be due to an increase in B-cell activating factor (BAFF) levels and lead to a disease flare. Future assessment of BAFF levels in patients stopping belimumab therapy and clinical correlation may support this hypothesis. Further studies are needed to confirm this observation. 10.3109/03009742.2015.1074277
    Refractory chylous pleural effusion with systemic lupus erythematosus : Surgical treatment when steroid/immunosuppressant resistant. Song Peng,Zhang JingCheng,Shang CongCong,Zhang Li Zeitschrift fur Rheumatologie We analyzed four cases of systemic lupus erythematosus (SLE) with chylous pleural effusion treated in our hospital from June 2013 to May 2017. The three females and one male ranged in age from 22 to 33 years. The length of disease course was 20 to 120 months. Treatment with glucocorticoids and immunosuppressants (cyclophosphamide or cyclosporine A) did not reduce chylous pleural effusion. Lymphatic obstruction was found in all patients after direct lymphangiography and the pleural effusion was significantly reduced after surgery. A literature search identified six previously reported patients with SLE and chylous pleural effusion. Five were sensitive to classic immunosuppression treatment, probably due to early intervention. However, as shown here, the thoracic duct can be involved in SLE, leading to an intractable chylous pleural effusion with no response to medical treatment. Surgery would be a better choice when lymphatic mechanical obstruction is found. 10.1007/s00393-018-0545-z
    Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus. So Min Wook,Koo Bon San,Kim You Jae,Kim Yong-Gil,Lee Chang-Keun,Yoo Bin Modern rheumatology High-dose steroids, immunosuppressants such as cyclophosphamide and cyclosporine, and high-dose intravenous immunoglobulin have all been used to control hemophagocytic lymphohistiocytosis (HLH) or autoimmune hemolytic anemia (AIHA) associated with systemic lupus erythematosus (SLE); however, some patients are refractory to treatment. Rituximab has successfully resolved many of the refractory manifestations of SLE. Here, we report a case of HLH and AIHA associated with SLE that was refractory or intolerable to conventional therapy, but was successfully treated with rituximab. 10.3109/14397595.2013.874740
    Successful treatment of a patient with refractory immune thrombocytopenic purpura in systemic lupus erythematosus with rituximab. Abe Kazuya,Ishikawa Yuichi,Ishikawa Junichi,Fujiwara Michio,Kita Yasuhiko Immunological medicine Immune thrombocytopenic purpura (ITP) is one of the complications of systemic lupus erythematosus (SLE). Although corticosteroids are usually selected for initial therapy, some patients are corticosteroid-resistant and, therefore, require other immunosuppressants or splenectomy. However, the best treatment approach in such patients remains unknown, and there is little evidence regarding which immunosuppressive agent can provide best results. We report the case of a patient with corticosteroid-resistant SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab (RTX). RTX might be a therapeutic option for corticosteroid-resistant SLE-ITP. 10.1080/25785826.2019.1696644
    A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab. Satoh Y,Nakano K,Yoshinari H,Nakayamada S,Iwata S,Kubo S,Miyagawa I,Yoshikawa M,Miyazaki Y,Saito K,Tanaka Y Lupus It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved. 10.1177/0961203318762598
    A case of developing progressive multifocal leukoencephalopathy while using rituximab and mycophenolate mofetil in refractory systemic lupus erythematosus. Ishikawa Yuichi,Kasuya Tadamichi,Ishikawa Junichi,Fujiwara Michio,Kita Yasuhiko Therapeutics and clinical risk management Progressive multifocal leukoencephalopathy (PML) is a central nervous system infection caused by John Cunningham (JC) virus reactivation in an immunocompromised patient. PML has various neurologic symptoms and has very poor prognosis. A 36-year-old man developed transverse myelitis and had a psychiatric disorder at the age of 26. He was diagnosed with systemic lupus erythematosus (SLE) and neuropsychiatric SLE (NPSLE), on the basis of leukopenia and presence of anti-DNA and anti-nuclear antibodies. Treatment with glucocorticoid (GC) was started, and remission was introduced. Six months before PML onset, his condition was complicated with hemophagocytic lymphohistiocytosis (HLH) due to exacerbation of SLE. Remission re-induction therapy by GC, cyclosporine-A, intravenous cyclophosphamide, and rituximab (RTX) was initiated and HLH improved. However, interleukin-6 levels of the cerebrospinal fluid (CSF) continued to rise. We thought that the disease activity of NPSLE worsened; thus, we introduced mycophenolate mofetil (MMF) 4 months before the PML onset. He developed progressive dysarthria and right hemiplegia. He was diagnosed with PML via magnetic resonance imaging and JC virus polymerase chain reaction in CSF. Considering that immunosuppressants, including RTX and MMF, are precipitating factors of PML, we discussed the RTX removal using plasma exchange (PEx), but we did not introduce PEx, because it was expected that the concentration of RTX was already lowered when he was diagnosed with PML. Treatment for PML with mefloquine and mirtazapine saved his life, but severe residual disabilities remained. This is the first report of a patient who developed PML during combination therapy with RTX and MMF. 10.2147/TCRM.S167109
    Therapeutic plasma exchange in paediatric SLE: a case series from India. Prasun Giri P,Sinha R,Pal P,Sarkar B Lupus Therapeutic plasma exchange (TPE) has been reported to be a useful adjunct in severe systemic lupus erythematosus (SLE) but paediatric literature continues to be scanty. We hereby present three cases of refractory paediatric SLE (pSLE) with thrombotic thrombocytopenic purpura (TTP), diffuse alveolar haemorrhage (DAH) and crescentic glomerulonephritis which were treated with TPE as an adjunctive therapy. TPE was carried out in haemodialysis units using the membrane filtration technique. Demonstrable benefit of TPE was seen in all three cases. In refractory pSLE, TPE may be a useful tool and should be considered. The report additionally highlights the feasibility of undertaking TPE in haemodialysis units, which is important as haemodialysis units are more readily available than dedicated apheresis units in developing countries. 10.1177/0961203315573346
    Successful treatment of refractory lupus nephritis by the sequential use of rituximab and belimumab. Simonetta Federico,Allali Danièle,Roux-Lombard Pascale,Chizzolini Carlo Joint bone spine 10.1016/j.jbspin.2016.01.008
    Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation. Marijanovich Nicole,Halalau Alexandra Case reports in rheumatology Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation. 10.1155/2018/7635982
    Safety and efficacy of thrombopoeitin mimetics for refractory immune thrombocytopenia purpura in patients with systemic lupus erythematosus or antiphospholipid syndrome: a case series. Lusa A,Carlson A Lupus Background While thrombopoeitin (TPO) agonists that act to simulate platelet production have been approved for use in steroid-refractory chronic immune thrombocytopenia purpura (ITP), there are few data on the safety and efficacy of these medications in patients with concurrent systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Given that these agents can increase all hematopoietic cell lineages, it is unclear if there is an increased risk for exacerbation of the underlying lymphocyte-driven autoimmune disease in this population. Case summaries This case series includes four patients with SLE, one with concurrent APS, who were treated for steroid-refractory ITP with TPO mimetics at the University of Virginia between 2005 and 2015. In three of the four cases the medication was successful in improving platelet counts and preventing bleeding events. In addition, none of the patients experienced thrombosis or worsening of their underlying autoimmune disease. Conclusions This case series suggests that TPO mimetics are safe and moderately effective in patients with ITP in the setting of SLE or APS and do not contribute to increased disease activity. 10.1177/0961203318770023
    Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia. Wang Q,Qian S,Li J,Che N,Gu L,Wang Q,Liu Y,Mei H Lupus Autologous hematopoietic stem cell (HSC) and mesenchymal stem cell (MSC) transplantation is currently being evaluated as a novel treatment for autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we report a case of autologous HSC transplantation combined with MSCs in a 25-year-old severe SLE patient with multiple life-threatening complications and refractory to conventional cyclophosphamide (CYC) therapy. After being pretreated with CYC, fludarabine and antithymocyte globulin, the patient was transplanted with autologous CD34+HSCs and MSCs by intravenous infusion. Hematopoietic regeneration was observed on day 12 thereafter. After HSC and MSC transplantation, the patient's clinical symptoms caused by SLE were remitted, and the SLEDAI score decreased. Moreover, CD4+CD25+FoxP3+Treg cells increased in peripheral blood mononuclear cells (PBMCs) after transplantation. This result suggests that the combined transplantation of HSCs and MSCs may reset the adaptive immune system to re-establish self-tolerance in SLE. A 36-month follow-up showed that the clinical symptoms remained in remission. Although a longer follow-up is required for assessing the long-term efficacy, our present results suggest that the combined transplantation of HSCs and MSCs may be a novel and effective therapy for refractory SLE. 10.1177/0961203315583541
    Successful treatment of refractory systemic lupus erythematosus using proteasome inhibitor bortezomib followed by belimumab: description of two cases. Sjöwall C,Hjorth M,Eriksson P Lupus Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab. The patients were carefully monitored with regard to disease activity and renal function. Anti-dsDNA and anti-C1q antibodies, complement proteins and lymphocyte subsets were analysed in consecutive samples. In December 2016, the patients had been in clinical remission post bortezomib administration for a period of 28 and 22 months, respectively. Potential benefits of using belimumab as maintenance therapy to prevent regeneration of autoreactive B cell clones are discussed. 10.1177/0961203317691371
    Protein-losing enteropathy associated with refractory systemic lupus erythematosus with a good response to rituximab. Sansinanea Pierina,Carrica Sebastián Augusto,Marcos Josefina,García Mercedes Argentina Reumatologia clinica A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission. 10.1016/j.reuma.2015.01.009
    Association of severe and therapy-refractory systemic lupus erythematosus and neuromyelitis optica: a management challenge. Furtado Inês,Pinheiro Guiomar,Campar Ana,Mendonça Teresa BMJ case reports Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder. Neuromyelitis optica (NMO) is an infrequent neuroinflammatory disorder, whose association with SLE remains rare. The authors report the case of an 18-year-old woman, with SLE refractory to multiple immunosuppressive therapies and novel biological agents. Under immunosuppressive therapy, the patient presented with transverse myelitis with contiguous spinal cord lesions and urinary incontinence, having been diagnosed with seropositive NMO, which was also proven to be refractory to common treatments. Partial recovery of the neurological deficits occurred with plasmapheresis, although not averting the brain involvement by NMO that ensued. The patient was listed nationally for allogeneic bone marrow transplant, but, unfortunately, no match was found and the patient died of severe cerebral NMO flare with coma due to brain swelling and consequent respiratory failure. Although the association of SLE and NMO is very rare, early diagnosis is crucial to facilitate initiation of immunosuppressive therapy. 10.1136/bcr-2017-222139
    Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature. Abu-Hishmeh Mohammad,Sattar Alamgir,Zarlasht Fnu,Ramadan Mohamed,Abdel-Rahman Aisha,Hinson Shante,Hwang Caroline The American journal of case reports BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. CASE REPORT We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet count in the following weeks. CONCLUSIONS Thrombotic thrombocytopenic purpura is a life-threatening hematological emergency which must be diagnosed and treated in a timely manner. Refractory cases of TTP have been described in the literature, but without clear evidence-based guidelines for its management, and is solely based on expert opinion and previous case reports. Further studies are needed to establish guidelines for its management. We present this case to highlight the role that cyclophosphamide might carry in those cases and to be a foundation for these future studies. 10.12659/ajcr.898955