A case report of successful treatment with plasma exchange for adult‐onset Still's disease with autoimmune hepatitis

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease is characterized by typical spiking fever with evanescent rash, sore throat, polyarthralgias or polyarthritis, and involvement of various organs. Most of the reported cases with liver involvement occurred during the period of treatment with hepatotoxic drugs, whereas AOSD associated autoimmune hepatitis (AIH) is extremely rare. AIH may be an indicator of the poor prognosis of AOSD. Herein we describe a case of successful treatment with plasma exchange for AOSD‐associated AIH. J. Clin. Apheresis 2010. © 2010 Wiley‐Liss, Inc.     

Adult-onset Still's disease—pathogenesis,clinical manifestations,and new treatment options

Abstract

Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a heterogeneous entity, usually presenting with high fever, arthralgia, skin rash, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. The diagnosis is clinical and empirical, where patients are required to meet inclusion and exclusion criteria with negative immunoserological results. There are no clear-cut diagnostic radiological or laboratory signs. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required.

Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control.

The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD.     

Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange

Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. J. Clin. Apheresis 30:46–49, 2015. © 2014 Wiley Periodicals, Inc.     

Atypical adult-onset Still’s disease with an initial and sole manifestation of liver injury: A case report and review of literature

BACKGROUNDAdult-onset Still''s disease (AOSD) typically presents with a high spiking fever, polyarthritis, transient maculopapular rash, neutrophilic leukocytosis, and hepatosplenomegaly. It has a wide spectrum of clinical symptoms ranging from mild to severe, with extensive involvement of almost every organ. Although liver involvement in the form of increased hepatic enzymes and bilirubin is common, no AOSD case with liver involvement as the initial manifestation of AOSD has been reported. CASE SUMMARYA 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week. Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level. Given that the clinical examination was unremarkable, liver biopsy was considered because the patient had a history of AOSD 6 years ago. Liver histopathology revealed that most hepatic lobules were still recognizable. Fusional necrosis was observed around most central veins. A few bridging necrotic zones were also found. Infiltration of multiple plasma cells were observed in the necrotic zone, and the reticular scaffold was still expanded. Additionally, no obvious fibrosis was observed in the portal area. Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area. Further examination was unremarkable except for a remarkably high level of ferritin. Collectively, a presumptive diagnosis of liver injury secondary to AOSD was made. The hepatic involvement responded well to glucocorticoid treatment.CONCLUSIONThis case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD. The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases. A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.     

The levels of macrophage migration inhibitory factor as an indicator of disease activity and severity in adult-onset Still's disease

Objectives:This study investigated the levels of macrophage migration inhibitory factor (MIF) in adult-onset Still's disease (AOSD) and explored the role of this pro-inflammatory cytokine in the systemic inflammation of AOSD.Design and methods:Serum MIF levels were measured by ELISA in patients with AOSD and controls. Intracellular MIF production by peripheral blood leukocytes was detected by three-color flow cytometry.Results:Serum MIF levels were significantly increased in patients with AOSD. Serum MIF levels were significantly higher in AOSD patients with sore throat, myalgias, splenomegaly, or pleuritis, and were closely correlated with clinical disease severity and activity. Examined by flow cytometry, the intracellular MIF levels in monocytes and T-lymphocytes from AOSD patients were significantly higher than those from healthy subjects.Conclusion:These data represent the first demonstration of increased MIF expression in AOSD, and suggest that MIF may be an important marker for disease evaluation and monitoring.     

Successful treatment of adult-onset still disease caused by pulmonary infection-associated hemophagocytic lymphohistiocytosis: A case report

BACKGROUND Adult-onset still disease(AOSD) and hemophagocytic syndrome(HPS) are two inflammatory diseases with very similar clinical manifestations. HPS is one of the most serious complications of AOSD and its risk of death is very high. It is difficult to identify HPS early in patients with AOSD, but early identification and proper treatment directly affects the prognosis.CASE SUMMARY A 39-year-old male showed a high spiking fever and myalgia. Laboratory data revealed elevated white blood cell, serum ferritin, and neutrophil percentage.However, his fever failed to relieve after a clear diagnosis of AOSD caused by pulmonary infection and treatment by antibiotics and corticosteroids;further laboratory data showed elevated serum ferritin, C-reactive protein, erythrocyte sedimentation rate and triglyceride, as well as liver abnormalities. Bone marrow smear showed hemophagocytosis. Secondary HPS was definitely diagnosed. The high fever disappeared and the laboratory findings returned to normal values after treatment by high-dose intravenous methylprednisolone and methotrexate.CONCLUSION For AOSD patients with high suspicion of HPS, active examination needs to be considered for early diagnosis, and timely using of adequate amount of corticosteroids is the key to reducing risk of HPS death.     

Adult-onset Still's disease

Background: Adult‐onset Still's disease (AOSD) is a febrile disorder of unknown aetiology characterised by typical spiking fever, evanescent rash, arthralgia and leucocytosis. Methods: According to the diagnostic criteria of AOSD, we identified 84 patients between 1990 and 2003. The aim of this study was to analyse the characteristics of AOSD in Turkish patients who were followed‐up in a tertiary referral centre. Results: Of 84 patients of AOSD, 59 (70.2%) were female, 25 (29.8%) were male. Arthralgia (96.4%), fever (95.2%), arthritis (69%), sore throat (65.5%) and typical rheumatoid rash (59.5%) were the most common findings. The mean value of laboratory findings were as follows; C‐reactive protein level of 11.59 ± 6.81 mg/dl, erythrocyte sedimentation rate (ESR) of 89.05 ± 31 mm/h, leukocyte count of 16,234.51 ± 7785.2/μl. Leucocytosis was present in 69 patients (84.15%). Forty‐eight patients had a WBC count ≥ 15,000/μl. Hypoalbuminaemia was present in 35 patients. Abnormal levels of aspartate aminotransferase and alanine aminotransferase were observed in 30 patients, whereas abnormal levels of alkaline phosphatase in 16 patients. Thirty‐seven patients had an ESR value of more than 100 mm/h. Thirty‐two patients had a ferritin value of more than 1000 ng/dl. Conclusion: High fever, sore throat, rheumatoid rash, polyarthritis, hyperferritinaemia (≥ 1000 ng/ml), leucocytosis with a neutrophilic predominance, anaemia and hypoalbuminaemia were remarkable observations in the initial examination.     

Thrombotic thrombocytopenic purpura precipitated by thyrotoxicosis

Thrombotic thrombocytopenic purpura (TTP) may be seen in association with autoimmune disorders such as immune hemolytic anemia and systemic lupus erythematosus, but rarely has it been associated with Graves' disease. We report one such case of a woman with new‐onset thyrotoxicosis caused by Graves' disease, who abruptly developed TTP, confirmed by low serum ADAMTS‐13 value. She had a dramatic response to plasma exchange, with remission of TTP. Definitive treatment with radioactive iodine resulted in euthyroidism and has prevented recurrence of TTP. J. Clin. Apheresis 27:265–266, 2012. © 2012 Wiley Periodicals, Inc.     

成人斯蒂尔病诊断与治疗

成人斯蒂尔病（AOSD）是一种自身免疫性风湿病，临床上以发热、关节痛、皮疹、白细胞增高为主要特征，实验室检查主要显示非特异性的炎症反应。非甾体抗炎药联合激素治疗AOSD取得了较好的疗效。本文就AOSD的诊断和治疗进行阐述。     

Tocilizumab for the treatment of adult-onset Still’s disease

Introduction: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation.

Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD.

Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.     

Ferritin,fever, and frequent visits: Hyperferritinemic syndromes in the emergency department

Fever of unknown origin (FUO) is defined as persistent fevers without an identifiable cause despite extensive medical workup. Emergency physicians caring for patients reporting a persistent, nonspecific, febrile illness should carefully consider potentially serious non-infectious causes of FUO. We present a case of a 35-year-old man who presented to the emergency department (ED) three times over a 10-day period for persistent febrile illness and was ultimately diagnosed with Adult-Onset Still's Disease (AOSD) after a serum ferritin level was found to be over 42,000 μg/L. AOSD, along with macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock comprise the four hyperferritinemic syndromes. These are potentially life-threatening febrile illnesses that characteristically present with elevated ferritin levels. In this article, we highlight the value of a serum ferritin level in the workup of a patient with prolonged febrile illness and its utility in facilitating early diagnosis and prompt treatment of hyperferritinemic syndromes in the ED.     

The role of damage-associated molecular pattern for pathogenesis and biomarkers in adult-onset Still’s disease

Introduction: Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease, which presents itself as an adult form of systemic juvenile idiopathic arthritis. Innate immune activation driven by a combination of genetic and environmental factors is the primary mechanism underlying disease pathogenesis in AOSD patients. Few biomarkers have been identified for AOSD diagnosis or for the assessment of disease activity or prediction of clinical outcomes. Damage-associated molecular patterns (DAMPs) can activate innate immunity, resulting in tissue damage. Changes in several DAMPs are associated with disease pathogenesis in AOSD patients.

Areas covered: This review describes the role of DAMPs in AOSD pathogenesis and discusses their potential for use as disease biomarkers. Together with overall pathogenesis of AOSD, high-mobility group box-1, advanced glycation end products, S100 proteins, and neutrophil extracellular traps are introduced and discussed in detail.

Expert opinion: The activation of macrophages and neutrophils is associated with several DAMPs, causing high concentrations of proinflammatory cytokines in AOSD patients. Involvement of certain DAMPs in AOSD patients is well documented due to the presence of sterile inflammation; however, direct evidence for some DAMPs is lacking. Further research into the role of DAMP molecules in AOSD patients may reveal new biomarkers and provide targets for disease intervention.     

What is the best sequence of chemotherapy in advanced colorectal cancer? Final results of a five-arm study

One hundred and ninety-three patients were assigned to receive 5-FU/LV, irinotecan and oxaliplatin in five different sequential treatment groups: Mayo Clinic Regimen (MCR) + LV5FU2 (group A); MCR + irinotecan (350 mg/m(2)) (group B); MCR + FOLFIRI (group C); MCR + FOLFOX4 (group D); FOLFIRI + FOLFOX4 (group E). The results were as follows: group A (32 patients), median overall survival (OS) 14 months, median time to progression (TTP1) 6 months, median TTP2 5 months, response rate (RR1) 22%, RR2 25%; group B (27 patients), OS 11 months, TTP1 6 months, TTP2 3 months, RR1 22%, RR2 19%; group C (43 patients), OS 14 months, TTP1 5 months, TTP2 5 months, RR1 12%, RR2 19%; group D (45 patients), OS 15 months, TTP1 5 months, TTP2 4 months, RR1 18%, RR2 20%; group E (46 patients), OS 19 months, TTP1 9 months, TTP2 5 months, RR1 39%, RR2 25%. There was a significant difference in OS (p < 0.005) between groups E vs. B and A, D vs. B. Sequential therapy with 3 active drugs (FOLFIRI + FOLFOX4) was the most efficacious combination in comparison with any other two drug combinations applied in our study.     

Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin‐induced TTP

The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin‐induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473–475, 2016. © 2015 Wiley Periodicals, Inc.     

Successful management of a Jehovah's Witness with thrombotic thrombocytopenic purpura unwilling to be treated with therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease treated successfully with plasma exchange. Jehovah's Witnesses whose religious beliefs preclude them from accepting plasma exchange may require alternative forms of therapy. We report a case of one such patient who presented with TTP, whom we successfully managed with vincristine and responded favorably without the need for plasma exchange.     

Hyponatraemia due to renal proximal tubule dysfunction in a patient with adult-onset Still's disease

Sir, Adult-onset Still's disease (AOSD) is a systemic inflammatorydisorder characterized by spiking fever, evanescent rash andmultiple organ involvements. Renal involvement has been, however,rarely reported in AOSD. We report an unusual occurrence ofproximal tubular dysfunctions presenting with hyponatraemiain a patient with AOSD. A 56-year-old Japanese man was admitted after 1 week of high-gradeintermittent fever, arthralgias and myalgias. Physical examinationrevealed polyarthritis and     

The Impact of Accreditation on Nursing Transition Into Practice Residency Programs

The evidence is clear: transition to practice (TTP) residency programs are essential for new graduate nurses (NGNs) entering the profession, for effective organizational efficiency, and for enhanced, safe patient care. Meanwhile, some nurse leaders struggle to inspire others, including chief executive and financial officers, to invest in TTP residency programs, and some nurse leaders are not convinced of the value. In this article, we reinforce the case for TTP residency programs and the impact of their being accredited. We do so by offering an example of a health care system's experience standardizing a TTP across 7 states (53 acute care hospitals). Furthermore, we offer a model to demonstrate how accredited programs benefit nurses and organizations by having a significantly lower turnover rate than nonaccredited programs. Finally, this article offers concrete actions that nurse leaders can take to ensure a safe and meaningful journey for new graduate nurses entering our profession.     

Patients with thrombotic thrombocytopenic purpura commonly develop metabolic alkalosis during therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) and myasthenia gravis (MG) are category I indications for therapeutic plasma exchange (TPE). This study was based on the hypothesis that the development of metabolic alkalosis during TPE is more common in TTP than in MG, based on our previous observations. In order to test it, we compared the levels of bicarbonate and potassium in both groups of patients undergoing plasmapheresis. Fifteen patients with TTP (190 procedures) and ten MG patients seen concurrently were studied. While baseline bicarbonate levels were similar among all patients, the post‐procedure bicarbonate levels in TTP patients were mostly elevated with a mean ± SD of 29.4 ± 3.5 mEq/L, as opposed to decreased or unchanged in MG patients 26.3 ± 3.1 mEq/L (mean ± SD) (P = 1.4 × 10^?8). Furthermore, alkalosis in the TTP group persisted throughout subsequent daily treatments. There was also a significant decrease between pre‐ and post‐TPE potassium levels in TTP patients (P = 3 × 10^?21) by paired Student's t test. Additionally, samples with levels <3.3 mEq/L were alkalotic 75% of the time. In the MG group, however, potassium was normal in 85% and 83% of the pre‐ and post‐TPE samples, respectively. Consequently, the hypokalemia was significantly more marked in the TTP group (P = 0.0008). These data confirm that plasmapheresis commonly induces metabolic alkalosis in TTP patients, probably due to high citrate in fresh frozen plasma, the frequency of treatments, and perhaps decreased renal clearance due to disease involvement of the kidneys. J. Clin. Apheresis. 16:120–124, 2001. © 2001 Wiley‐Liss, Inc.     

Thrombotic thrombocytopenia purpura: A single institution experience

TTP is a disease with protean manifestations leading to errors in diagnosis. Critical reevaluation of a single observer's experience at LIJMC over a 7-year period is compared to that in published literature. We retrospectively analyzed presentation, clinical course, treatment, and outcome of 15 patients treated for TTP between 1990 and 1997 by one of the authors (V.C.). Minimal diagnostic criteria for TTP were unexplained moderate to severe thrombocytopenia (platelet count <100,000/cmm), microangiopathic hemolytic anemia, with or without low grade fever, and no other attributable etiologies. Neurologic and/or renal dysfunction constituted severe grade. Age range was 5–86 years, with one patient age 5, the youngest yet to date reported with classic TTP. Female to male ratio was 2:1. Overall survival rate was 87%; 40% of patients experienced immediate relapse within the first 4 weeks of presentation; and predisposing causes for immediate relapse appear to be intercurrent infections and severity of presentation. There was a 40% incidence of late relapses of TTP. Two patients with an unusually high number of late recurrences (6 and 16) were HCV-Ab positive and the possible role of persistent HCV infection in recurrent TTP was explored. J. Clin. Apheresis 14:9–13, 1999. © 1999 Wiley-Liss, Inc.