A case report of fulminant cytokine release syndrome complicated by dermatomyositis after the combination therapy with immune checkpoint inhibitors

Introduction: Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs. Patient concerns: A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24 mg/dL; CK, 40, 500 U/L; D-dimer, 290 μg/mL; ferritin, 329, 000 ng/mL. Diagnosis: CRS induced by ICI combination therapy. Interventions: Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins. Outcomes: The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month. Conclusion: Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroid-resistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective

BALB/c-Fcgr2b−/−Pdcd1−/− mouse expressing anti-urothelial antibody is a novel model of autoimmune cystitis

We report the impact of anti-urothelial autoantibody (AUAb) on urinary bladder phenotype in BALB/c mice deficient of the FcγRIIb and PD-1. AUAb was present in serum samples from approximately half of the double-knockout (DKO) mice, as detected by immunofluorescence and immunoblots for urothelial proteins including uroplakin IIIa. The AUAb-positive DKO mice showed degeneration of urothelial plaque and umbrella cells, along with infiltration of inflammatory cells in the suburothelial layer. TNFα and IL-1β were upregulated in the bladder and the urine of AUAb-positive DKO mice. Voiding behavior of mice was analyzed by the Voided Stain on Paper method. 10-week-old and older AUAb-positive DKO mice voided significantly less urine per void than did wild type (WT) mice. Furthermore, administration of the AUAb-containing serum to WT mice significantly reduced their urine volume per void. In summary, this report presents a novel comprehensive mouse model of autoimmune cystitis

抗尿路上皮抗体を発現するBALB/c-Fcgr2b-/-Pdcd1-/-マウスは自己免疫性膀胱炎の新しいモデルである

京都大学0048新制・課程博士博士(医学)甲第17096号医博第3704号新制||医||994(附属図書館)29826京都大学大学院医学研究科外科系専攻(主査)教授 三森 経世, 教授 柳田 素子, 教授 生田 宏一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Underweight body mass index is a risk factor of mortality in outpatients with nocturia in Japan

Background: Although nocturia has been reported to increase mortality in elderly individuals, the particular risk factors that are associated with this event are unclear. Therefore, we evaluated risk factors for death in outpatients with nocturia. Methods: Between October 2002 and December 2009, 250 consecutive patients with nocturia were enrolled in two general hospitals in Japan. Among them, 193 patients were able to be followed for at least 1 year and up to 9 years (median 4.8 years) if the patients did not die. Mortality rates and risk factors were evaluated in the nocturic outpatients. Results: Two- and 5-year survival of the nocturic outpatients was 94.6 % [95 % confidence interval (CI) = 92.2-97.1] and 82.6 % (95 % CI = 75.4-87.8), respectively. Higher Charlson Comorbidity Score, lower body mass index (BMI) and lower Physical Component Summary of Short Form-36 item scores were significantly correlated with mortality (p < 0.0001, p < 0.005 and p < 0.05, respectively) in multivariate analysis. The International Prostate Symptom Score, Pittsburgh Sleep Quality Index, Mental or Role/Social Component Summary of Short Form-36 item scores and Nocturnal Polyuria index were not significantly correlated with mortality. The mortality rate was significantly higher in subjects with an underweight BMI (<18.50) compared with a normal range (18.50-24.99) or overweight (≥25.00) BMI [p < 0.00005, hazard ratio (HR) = 5.84, 95 % CI = 2.03-16.8; p < 0.0005, HR = 5.92, 95 % CI = 1.94-18.0]. Conclusions: Additional attention is required for nocturic outpatients with not only a high Charlson Comorbidity Score but also an underweight BMI because of their high mortality. Large prospective studies are warranted to validate this finding and extend more