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Vascular endothelial growth factor inhibitors and checkpoint inhibitors are effective treatments for solid tumors. These new classes of anti-cancer agents frequently cause kidney-related side effects. Although their anti-cancer effects may be enhanced when used in combination, the severity of their kidney-related side effects is unknown. We herein report the first case of thrombotic microangiopathy and mesangial proliferative glomerulonephritis caused by combined treatment with atezolizumab and bevacizumab in a 74-year-old man with hepatocellular carcinoma. The combination therapy was discontinued and replaced with intravenous methylprednisolone followed by oral prednisolone. Subsequently, the urinary protein excretion levels declined.

A 58-year-old woman with a history of Sjogren’s syndrome was admitted to our hospital with cough, decreased right lung breath sounds and arthralgia in both thumbs. Chest computed tomography showed consolidation with air bronchogram in the right lung. Levels of anti-cyclic citrullinated peptide antibody and rheumatoid factor levels were significantly elevated. She was diagnosed with rheumatoid arthritis induced by bacterial organizing pneumonia. Treatment with salazosulfapyridine was added for rheumatoid arthritis and arthralgia gradually improved. This case highlights that respiratory infections could lead to anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis in patients with Sjogren’s syndrome.

Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and hypoalbuminemia. This condition is caused by leakage of plasma and proteins into the extravascular space and can be classified as either idiopathic or secondary. Secondary systemic capillary leak syndrome can result from cancer, infections, medications, or surgery. Systemic capillary leak syndrome frequently develops as a side effect of denileukin diftitox treatment of refractory cutaneous T-cell lymphoma. However, the pathophysiology of this disease is not well understood. Herein, we report a case of denileukin diftitox-induced systemic capillary leak syndrome.

Lumbar hernias are extremely rare. The posterolateral abdominal wall has two susceptible areas - the superior (Grynfeltt-Lesshaft's triangle) and the inferior (Petit's triangle) lumbar triangles - that cause superior and inferior lumbar hernias, respectively. We herein report a 67-year-old woman with nephrotic-range proteinuria caused by primary superior lumbar hernia. Superior lumbar hernias should be considered as a differential disease causing massive orthostatic proteinuria in adults. The present case highlights the importance of considering lumbar hernia in patients with flank swelling and the potential complications that may result from a missed diagnosis.

Livedo reticularis occurs when there is increased visibility of the venous plexus, often caused by reduced arterial inflow or venodilation.

Background Zeb2, a zinc finger E-box-binding homeobox transcription factor, regulates transforming growth factor (TGF)-β signaling pathway. However, its role in the pathogenesis of acute kidney injury (AKI) and AKI-to-chronic kidney disease (CKD) transition is unclear. Methods We evaluated Zeb2 function in a bilateral renal ischemia–reperfusion injury (IRI)-induced AKI model using proximal tubule-specific Zeb2 conditional knockout (Zeb2-cKO) and wild-type (WT) mice, and in renal biopsy samples. Results In Zeb2-cKO mice, the levels of plasma creatinine and blood urea nitrogen post-IRI were significantly lower than that in WT mice. Immunohistological analysis revealed mild tubular injury, reduced neutrophil infiltration, fewer fibrotic changes and reduced expression of fibrotic proteins [collagen type IV, α-smooth muscle actin (α-SMA), fibronectin and connective tissue growth factor (CTGF)], at 3–14 days post-IRI. Zeb2 expression was upregulated in proximal tubular cells post-IRI in WT mice. Zeb2 siRNA transfection reduced TGF-β-stimulated mRNA and protein expression of collagen type IV, α-SMA, fibronectin and CTGF in cultured renal tubular cells. Patients with AKI-to-CKD transition exhibited high Zeb2 expression in renal tubules, as revealed by renal biopsy. Hypoxia and CoCl2-treatment upregulated Zeb2 promoter activity and mRNA and protein expression in cultured renal tubular epithelial cells, suggesting a regulatory role for hypoxia. Conclusions Zeb2 was upregulated in renal tissues in both mice and humans with AKI. Zeb2 regulates fibrotic pathways in the pathogenesis of AKI and AKI-to-CKD transition. Therefore, inhibition of Zeb2 could be a potential therapeutic strategy for AKI.

We herein report the first case of lupus-related protein-losing enteropathy associated with pseudo-pseudo Meigs’ syndrome. Lupus-related protein-losing enteropathy and pseudo-pseudo Meigs’ syndrome are extremely rare complications in patients with systemic lupus erythematosus, Both have a similar clinical course characterized by producing marked ascites, and respond to steroids in typical cases. However, in our case, steroid monotherapy was inadequate and the addition of hydroxychloroquine was effective for their treatment. Furthermore, no reports have previously confirmed elevated CA 125 levels with lupus-related protein-losing enteropathy or increased 99mTc-HSA activity with pseudo-pseudo Meigs’ syndrome. In addition, we are the first to report an evaluation of the histopathology of lupus-related protein-losing enteropathy. Previously reported cases have been described as being caused by either pseudo-Meigs’s syndrome or lupus-related protein-losing enteropathy as the cause of the rare pathology that causes marked pleural effusion and ascites in patients with systemic lupus erythematosus, but it has not been evaluated whether the other is co-occurring. Our case highlights that there is a potential case of overlapping lupus-related protein-losing enteropathy and pseudo-Pseudo-Meigs’s syndrome. Furthermore, it is possible that patients with marked ascites with elevated CA 125 levels were mistakenly diagnosed with Meigs’s syndrome or pseudo-Meigs’s syndrome associated with malignant or benign ovarian tumors and underwent surgery. Clinicians should not forget SLE with pseudo-Pseudo-Meigs’s syndrome as one of the differential diagnoses for marked ascites with elevated CA 125 levels.

Polyarteritis nodosa (PAN) is a primary systemic necrotizing vasculitis predominantly targeting medium-sized arteries defined as the main visceral arteries and their branches. Central nervous system (CNS) involvement by PAN is rare. The findings in CNS involvement due to PAN include aneurysm formation and stenosis/occlusion of the intracranial carotid artery. Here, we present a very rare case of a patient who sustained repeated infarcts without abnormal inflammation marker levels. This was suggestive of thrombotic cerebral infarctions, perhaps due to malignancy. This case is an important reminder to rheumatologists and neurologists to consider the diagnosis of PAN in the workup of repeated infarcts, even in the absence of systemic inflammatory markers, and to be vigilant in assessing any skin lesions.

A 45-year-old man presented with fatigue for the previous two days. Because of severe hypoxemia and chest radiograph showing severe consolidation only in the right lung field, he was admitted to a near-by district hospital under the diagnosis of acute pneumonia. Since his respiratory condition rapidly deteriorated, he was transferred to our hospital. The diagnosis of unilateral cardiogenic pulmonary edema was made based upon the echocardiographic examination which showed severe mitral regurgitation secondary to chordal rupture of the posterior mitral valve leaflet (P2). After successful intensive medical treatment with diuretics and extracorporeal membrane oxygenation, mitral valve repair was performed with quadrangular resection of the posterior mitral leaflet (P2) and insertion of 28 mm Cosgrove ring. It is important to recognize acute and severe mitral regurgitation as a main cause of unilateral cardiogenic pulmonary edema. Prompt differentiation from acute pneumonia is critical to save lives of the patients.

Background:Adult-onset Still’s disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques.Objectives:This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.Methods:We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).Results:Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from haemophagocytic lymphohistiocytosis.Conclusion:Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.Disclosure of Interests:None declared

Objectives:To assess the clinical implications of ultrasonography (US) in monitoring disease activity and diagnosis of relapsing polychondritis (RP).Methods:Firstly, auricular (n=5) and nasal (n=1) chondritis of six patients with RP were assessed by US before and after treatments. The relationship between US findings and serum markers were evaluated. Moreover, the comparisons of US findings between the auricle of patients with RP (n=5), repeated trauma (n=5), cellulitis (n=2) and healthy subjects (n=5) were also assessed.Results:US finding before treatment showed low-echoic swollen auricular and nasal cartilage with increased power Doppler signals (PDS) in all cases of RP. US findings corresponded to biopsy findings. After treatment, the swollen ear and nose completely resolved. Then, US findings also showed dramatic reductions in swollen cartilage with the decrease in PDS. Although serum markers completely improved, US finding remained in 1 of 6 cases, and this case showed flare due to PSL tapering. Finally, RP could be differentiated from the damage of repeated trauma and cellulitis by the presence or absence of PDS and subperichondrial serous effusion.Conclusion:US of auricular and nasal cartilage in RP possibly facilitates evaluation of auricular lesions and monitoring of disease activity, especially when we consider the treatment response and the timing of drug tapering.Disclosure of Interests:None declared

Necrosis of the Fingers and Toes An 84-year-old main presented with discoloration and pain in the fingers and toes that had progressed over a 2-week period. Biopsy findings were consistent with a medium-vessel vasculitis.

Background Relapsing polychondritis (RP) is a rare systemic inflammatory disorder and might often be refractory. Therefore, the discovery of more convenient imaging modality than contrast-CT, MRI and FDG-PET/CT would be required on diagnosis and treatment. Objectives To assess the clinical implications of ultrasonography (US) in monitoring disease activity and diagnosis of relapsing polychondritis (RP). Methods Firstly, auricular chondritis of patients with RP (n=5) were assessed by US before and after treatments. Second, the relationship between US findings and other serum inflammatory markers were evaluated. Moreover, the comparisons of US findings between the auricle of patients with RP (n=5), repeated trauma (n=5) which is similar to auricle of RP, and healthy subjects (n=5) were also assessed. Results US finding before treatment showed low-echoic swollen auricular cartilage with increased power Doppler signals (PDS) in all cases of RP. US findings corresponded to biopsy findings. After treatment with prednisolone (PSL) combined with methotrexate, the swollen ear completely resolved. Then, US findings also showed dramatic reductions in swollen cartilage with the decrease in PDS. When serum inflammatory markers completely improved, but US finding remained in 1 of 5 cases, and this case showed flare due to PSL tapering. Finally, RP could be differentiated from the damage of repeated trauma with producing subperichondrial serous effusion. Conclusions US of auricular cartilage in RP possibly facilitates evaluation of auricular lesions and monitoring of disease activity, especially when we consider the treatment response and the timing of drug tapering. Disclosure of Interest None declared

Background Adult-onset Still’s disease (AOSD) is an acute and systemic inflammatory disorder that is characterised by high spiking fever, evanescent rash, arthralgia/arthritis and hyperferritinemia. However, recent reports showed that not only typical evanescent salmon-coloured rash but also atypical skin lesions, persistent pruritic papules and plaques, could be associated with AOSD. Objectives To assess the clinical significance of dyskeratotic cells (DCs) in skin lesions of AOSD. Methods We assessed histology of skin lesions including persistent pruritic skin lesions in Japanese patients with AOSD (n=15). Moreover, we compared histology of AOSD with dermatomyositis (DM) (n=6), drug eruptions (DE) (n=7), and graft versus host disease (GVHD) (n=6). Results AOSD with persistent pruritic skin lesions (n=10) histologically showed DCs only in upper layer of epidermis and horny layer without inflammatory cells infiltrations, indicating dyskeratosis. AOSD with evanescent rash (n=5) histologically showed no DCs. DCs were positive by ssDNA staining, suggesting apoptotic cells. Serum IL-18 showed significantly higher in AOSD patients with dyskeratosis (n=10) than without dyskeratosis (n=5). In contrast to AOSD with DCs, the histology of DM, DE and GVHD demonstrated that DCs existed in all layers of epidermis with inflammatory cells infiltrations. Conclusions Persistent pruritic skin lesions in AOSD are specific by prominent epidermal apoptosis involving the upper layers of epidermis. Moreover, hyper IL-18 might be related with dyskeratosis. Disclosure of Interest None declared

Background Intravesical instillation of Bacillus Calmette-Guerin (iBCG) is used as an effective immunotherapy of bladder cancer. However it may have, as adverse event, a reactive arthritis (ReA) and the frequencies are known as about 0.5% to 1% in Western countries. Objectives To evaluate the trend of incidence rate, frequency and HLA phenotype of reactive arthritis (ReA), uveitis and other adverse events in Japanese patients with bladder cancer following iBCG therapy. Methods The clinical findings of Japanese patients who received iBCG (n=555 [250 and 305 in Kochi Medical School Hospital and Kurashiki Medical Centre, respectively]) for bladder cancer from March 1997 to February 2017 were retrospectively assessed, with specific attention to patients with ReA and uveitis. HLA phenotypes of patients with ReA were also looked. Moreover, iBCG-induced ReA diagnosed from 1997 to 2007 were compared with that from 2007 to 2017. Finally, outcomes of ReA patients were also evaluated. Results Patients’ mean age was 72±10 years and male/female ratio was 438/117. Fever, haematuria, and dysuria were presented in 91/555 (16.4%), 121/555 (21.8%), and 196/555 (35.3%), respectively of all enrolled patients. Of the 555 cases, ReA and uveitis were revealed in 11/555 (2.0%) and 4/555 (0.7%). The protocol of iBCG therapy was stable over the 20 years. Notably, HLA-B27, -B35, -B39 and -B51 positivity was more frequent in ReA patients (9.1%, 36.3%, 36.3% and 63.6%, respectively) (p Conclusions The 2.0% iBCG-induced ReA frequency in Japanese patients exceeds that in Western countries, and its incidence has been stable and all ReA did not progress chronic type and SpA over the last 20 years. HLA phenotype, especially HLA-B51 and -B39 alleles in addition to -B27, may be a risk factor in iBCG-induced ReA in Japanese patients. Disclosure of Interest None declared