Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching. The patient underwent a dialytic treatment of hemodiafiltration with endogenous reinfusion. The technique uses the super-high-flux membrane Synclear 02 (SUPRA treatment) coupled with an adsorbent cartridge that has affinity for many toxins and mediators. Fever and joint pain were immediately reduced after treatment and, subsequently, there was a notable reduction of the skin damage. Prednisone and immunosuppressive drugs were gradually reduced until complete suspension. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer was performed for identification of proteins captured by a resin bed during a dialysis session of the patient. This technique identified several biomarkers of kidney injuries, uremic toxins, fragments of immunoglobulins, antigens involved in antiphospholipid syndrome and a new marker (α-defensin) that correlated significantly with disease activity. The removal of these different proteins could possibly provide an explanation of the improvement in the patient's symptoms and the normalization of her SLE. SUPRA coupled with an adsorption may be a promising new technique for the treatment of lupus nephritis.
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The purpose of the study was to collect and summarize baseline demographic, clinical, and laboratory characteristics in a large, diverse cohort of patients with HES and to review responses to treatment with conventional and novel therapies.
The effects of 10 glucocorticoids on cell viability were first assessed in three bladder cancer lines. Selected compounds were further assessed for their ability in cell viability and apoptosis, with or without cisplatin, as well as in cell invasion.
Leprosy is still an important and debilitating disease with a broad clinical spectrum. However, this disease occurs most often endemically, and as an imported disease it can also still be recognized in the nonendemic industrialized world.
Very low quality evidence from one trial suggests that hyperbaric oxygen therapy may be an effective treatment for moderate to severe Bell's palsy, but this study was excluded as the outcome assessor was not blinded to treatment allocation. Further randomised controlled trials are needed.
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Anti-type VII collagen autoantibodies are often detectable in patients with bullous systemic lupus erythematosus (BSLE). However, the timing of their appearance preceding the onset of disease is unknown to date.
Systemic juvenile idiopathic arthritis (SJIA) is one of the most severe forms of arthritis that affects children younger than 16 years of age at onset. SJIA often requires corticosteroids to control the inflammation. However, long-term corticosteroid use may have adverse effects, including intracranial hypertension (IH). Biologic therapies have been used as corticosteroid sparing agents. We report the first case of a child with steroid-dependent SJIA treated with tocilizumab, an IL-6 receptor monoclonal antibody, who developed fulminant IH, bilateral papilloedema and vision loss when oral prednisone was weaned from 2 to 1 mg per day. Despite repeated lumbar punctures and high dose acetazolamide, he required urgent unilateral optic nerve sheath fenestration (ONSF). This endoscopic surgical intervention released the pressure exerted by the cerebrospinal fluid on the optic nerve and stopped the progression of vision loss. Nine weeks after the diagnosis of bilateral papilloedema, his vision was completely restored in one eye and partially recovered in the contralateral one. Long-term treatment with corticosteroids even at very low dose and tocilizumab may predispose to severe IH, papilloedema and vision loss. The role that tocilizumab might have played in this case in unclear. Early recognition and prompt treatment of papilloedema is crucial in avoiding permanent vision loss. Fulminant papilloedema in an immunocompromised child carries additional significant challenges. Early ONSF is a safe and effective intervention in refractory papilloedema. Children with severe papilledema secondary to IH should be managed by a multidisciplinary team in tertiary centres.
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Newly diagnosed GCA was defined as diagnosis ≤6 weeks before baseline. Relapsing GCA was defined as diagnosis >6 weeks before baseline with ≥2 consecutive weeks of prednisone ≥40mg/day. All patients had active GCA within 6 weeks of baseline. All statistical results are exploratory.
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Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.
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Study COU-AA-302, ClinicalTrials.gov number, NCT00887198.
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We investigated the clinical characteristics and therapeutic of elderly patients (≥55) with acute lymphoblastic leukemia (ALL).
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We report the case of a patient with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) who exhibited sudden progression of lung infiltration while maintaining stable kidney function. The 69-year-old man was diagnosed with AAV and renal insufficiency 4 years ago. Pulmonic affectation was detected in the right lower lobe of lung by a computed tomography (CT) scan. After beginning cyclophosphamide pulse therapy and sequential therapy with low-dose prednisone, he underwent a 4-year follow-up to detect changes in hemoglobin levels and serum creatinine levels, and had chest CT examinations. The CT scan and creatinine assay showed stable pulmonic fibrosis and kidney function. Although there was no increase of creatinine and detectable perinuclear ANCA, the patient suffered a pulmonary hemorrhage and levels of hemoglobin became progressive lower; the lung infiltration was found to be enlarged compared to the last examination the previous year. After immunosuppressive therapy for one week, the lung fibrosis was progressive, increased pulmonary hemorrhage occurred, and the patient died due to respiratory failure but not end-stage renal failure.
In 49 patients with severe poison ivy, non-adherence rates, rash return, medication side effects, and time to improvement and complete healing of the rash were not significantly different between the two groups. Patients receiving the long course regimen were significantly less likely to utilize other medications (22.7% vs. 55.6%, P = 0.02, number needed to treat 3.05).
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There are many therapies available for the management of low-grade lymphoma. With follicular lymphoma, for example, combination of chemotherapy and rituximab (immuno-chemotherapy) and consecutive maintenance therapy for 2 years is the current standard of care. To date, the most widely used regimen seems to be rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Substitution of liposomal doxorubicin in place of conventional doxorubicin may improve outcomes in this indication, although evidence for its use in low-grade lymphoma is not as relevant as in aggressive lymphoma. Bendamustine, in combination with rituximab, has shown very good efficacy and tolerability in several lymphoma types, particularly follicular lymphoma and other low-grade lymphomas. Other combinations, such as those including bortezomib and lenalidomide, are under investigation in low-grade lymphoma, and the duration of rituximab maintenance therapy following bendamustine-rituximab-containing induction is being researched by the German Study Group for Indolent Lymphoma (StiL).
Nineteen children with a biopsy-proven TIN.
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Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.
The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors.
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Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine.
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In the ALL-BFM studies for treatment of acute lymphoblastic leukemia, reduction of leukemic blasts in peripheral blood after a one-week prednisone pre-phase - the so-called prednisone response - has been used for risk stratification since the 1980s and has been one of the most relevant factors for identification of high-risk patients. In the trial ALL-BFM 95, early cytomorphological marrow response on day 15 of induction therapy was prospectively evaluated and its prognostic value was analyzed in comparison to the prednisone response and other established prognostic factors.
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In individuals with nephrotic range proteinuria with a normal or low lipid profile status along with normal serum albumin levels, urine color and nature, frequency, and checking the urine for chyle can help identify the large subgroup who unnecessarily have to undergo kidney biopsy and at times are treated with immunosuppression, which is not only life threatening but useless in these patients.
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This case raises the question of authentic SSc and neoplasia and highlights the importance of capillaroscopy in the follow-up of SSc. The complete regression of SSc and of capillaroscopic abnormalities could be explained by the paraneoplastic nature of SSc or by the direct action of the chemotherapy and bone marrow transplantation.
Renal involvement by sarcoidosis in native and transplanted kidneys classically presents as non caseating granulomatous interstitial nephritis. However, the incidence of sarcoidosis in native and transplant kidney biopsies, its frequency as a cause of end stage renal disease and its recurrence in renal allograft are not well defined, which prompted this study. The electronic medical records and the pathology findings in native and transplant kidney biopsies reviewed at the Johns Hopkins Hospital from 1/1/2000 to 6/30/2011 were searched. A total of 51 patients with a diagnosis of sarcoidosis and renal abnormalities requiring a native kidney biopsy were identified. Granulomatous interstitial nephritis, consistent with renal sarcoidosis was identified in kidney biopsies from 19 of these subjects (37%). This is equivalent to a frequency of 0.18% of this diagnosis in a total of 10,023 biopsies from native kidney reviewed at our institution. Follow-up information was available in 10 patients with biopsy-proven renal sarcoidosis: 6 responded to treatment with prednisone, one progressed to end stage renal disease. Renal sarcoidosis was the primary cause of end stage renal disease in only 2 out of 2,331 transplants performed. Only one biopsy-proven recurrence of sarcoidosis granulomatous interstitial nephritis was identified.
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Seven female patients were studied. All were Caucasians, with a median age of 53 years and a median disease duration of 72 months. The median follow-up period was 14±4 months. During treatment period, no relapse of the disease occurred. All patients showed a favourable clinical response and reported a good tolerance to the treatment with an improved quality of life. CK serum levels decreased over time with a concomitant improvement in MRC and Rankin modified scores. Three patients were able to discontinue the immunosuppressant and all to reduce the daily maintenance prednisone dose.
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Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.
When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.
Sarcoidosis is a multisystem granulomatous syndrome of unknown etiology with noncaseating epithelioid granulomas being the pathognomonic pathological finding. Sarcoidosis most commonly involves the lungs and involvement of the gastrointestinal (GI) tract is uncommon. Pancreatic sarcoidosis is very rare, especially when it is the presenting feature of sarcoidosis and can masquerade as pancreatic cancer. Tissue infiltration in pancreatic sarcoidosis can lead to either a diffuse nodular appearance or a mass-like lesion. We present an interesting case of a 47-year-old woman with a 10-pack-year history of smoking who presented with sharp epigastric pain, weight loss, and elevated lipase level. CT and MRI imaging showed a 4 cm × 5 cm heterogeneous pancreatic mass with a dilated pancreatic duct and peripancreatic lymphadenopathy. Endoscopic ultrasound guided FNA revealed noncaseating granulomas with no evidence of malignancy or atypical infection. CT of the chest revealed bilateral mediastinal and hilar adenopathy with calcification, without any parenchymal abnormalities, and her angiotensin-converting enzyme level was elevated at 170 U/L. The clinical picture pointed to the diagnosis of pancreatic sarcoidosis. Given the severity of gastrointestinal symptoms related to pancreatic sarcoidosis, prednisone therapy at 0.5 mg/kg/day was initiated with complete resolution of symptoms at 8 weeks.
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We observe that increased TNF-α levels may be involved in rituximab-related acute pulmonary fibrosis.
Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic.
The objectives for this study were to evaluate trends in the medications prescribed for the management of lupus erythematosus (LE) and to assess how treatment varies among different specialists.