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Hepatic veno-occlusive disease (VOD) is a complication of haematopoietic stem cell transplantation. VOD is associated with the occurrence of thrombotic microangiopathy (TMA). In haematopoietic stem cell transplantation, VOD and TMA are endothelial syndromes resulting from endothelial cell activation and dysfunction. In rheumatic disease, while TMA is not rare, there are few reports of VOD. In idiopathic myositis, only one case with VOD and TMA complications has been reported, and there are no published cases in juvenile dermatomyositis (JDM). We report a case of JDM manifesting VOD and TMA complications during the treatment for myositis and macrophage activation syndrome (MAS). A 5-year-old boy diagnosed as anti-nuclear matrix protein 2 antibody–positive JDM was complicated by MAS. He received pulsed methylprednisolone, prednisolone, and tacrolimus, but JDM and MAS progressed. He was then treated with intravenous cyclophosphamide and cyclosporine A, with improvement in myositis symptoms and MAS. After initiation of cyclophosphamide and cyclosporine A, he developed haemolysis, painful hepatomegaly, liver damage, and ascites. He was diagnosed with VOD and TMA. Cyclophosphamide and cyclosporine A were discontinued, with recovery from VOD and TMA. The patient remained well on treatment with methotrexate, without any relapse of JDM and MAS to date. The presence of vasculopathy and hypercytokinaemia because of JDM and MAS exacerbated endothelial cell damage. In the present case, we suggest that the main cause of VOD was medication with CY and CsA, which had been used to treat acute exacerbation of MAS and JDM.

The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated.We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19.In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P 0.001 and r = 0.53, P 0.001, respectively).Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Thrombotic microangiopathy (TMA) is generally diagnosed through clinical features characterized as microangiopathic hemolytic anemia, thrombocytopenia, and multiple organ injury, as well as by pathological findings such as vascular damage and endothelial cell injury. Rheumatic and autoimmune diseases could be accompanied by secondary TMA; in fact, systemic lupus erythematosus (SLE) is a common disease associated with secondary TMA, and SLE complicated with TMA has been reported to have a poor prognosis. Although TMA occurs rarely in pediatric SLE patients, it often leads to severe clinical conditions. Here, we report a rare case of severe juvenile-onset SLE complicated with TMA and kidney injury. The 5-year-old patient showed renal dysfunction, thrombocytopenia, hemolytic anemia, nephrotic syndrome, hypocomplementemia, and elevation of anti-dsDNA IgG levels. Kidney biopsy revealed mesangial proliferation and endocapillary proliferation, as well as plumped endothelial cells, with full-house pattern deposits in immunofluorescence study. Combination treatment of methylprednisolone pulse therapy followed by oral prednisolone, mycophenolate mofetil, and plasma exchange was effective, whereas eculizumab did not show therapeutic effects. The patient further showed recurrent deterioration, and we initiated intravenous cyclophosphamide in addition to combination treatment and eventually succeeded in controlling the disease. Genome analysis by whole-exome sequencing revealed no particular gene mutation related to either complement disorders or type-1 interferon. Further elucidations concerning the pathogenic mechanisms causing juvenile-onset SLE are needed to establish an efficient treatment strategy for TMA with SLE.

Introduction: Thoracic aortic aneurysms and dissections (TAAD) are rare in children and often associated with underlying genetic disorders accompanied with other systemic manifestations, including connective or osteo-articular tissue diseases. Case Presentation: We report the case of a 10-year-old girl with a novel nonsense SMAD3 mutation, p.Glu102X, who presented with familial TAAD without any signs of osteoarthritis. Histological analysis of aorta fragments from the patient with TAAD obtained during surgery revealed elastin degradation and inflammatory infiltration of T cells with dense CD31 + microvessels, which is consistent with previous findings. Interestingly, the family members with the SMAD3 mutation developed IgA nephropathy. Conclusion: Because the TGF-β/Smad signalling pathway plays an important role in the primary pathogenesis of IgA nephropathy and TAAD, we presume that IgA nephropathy could be a novel clinical phenotype of SMAD3 deficiency. Further accumulation of genetically proven cases with SMAD3 deficiency is needed to more accurately characterize phenotypic variability and elucidate a wide spectrum of TGF-β-associated disorders.

Rationale: Intestinal Behçet disease (BD) with myelodysplastic syndrome (MDS) is a rare condition that is resistant to various immunosuppressive therapies. Several cases in which hematopoietic stem cell transplantation (HSCT) was effective for intestinal BD with MDS accompanying trisomy 8 have been reported. Patient concerns: We report an 18-year-old female with a 7-year history of BD. Colonoscopy demonstrated a huge ulcer in the cecum. Chromosomal examination revealed a karyotype of trisomy 8 in 87% of cells. Bone marrow examination revealed dysplastic cells in multilineages. Diagnoses: A diagnosis of intestinal BD associated with MDS accompanying trisomy 8 was made. Interventions: The patient underwent ileocecal resection due to microperforations of ileocecal ulcers; she then underwent allogeneic peripheral blood stem cell transplantation (PBSCT) with her mother as a donor. Outcomes: After the PBSCT, the patient's symptoms due to BD (fever, oral aphthae, abdominal pain, and genital ulcers) completely disappeared, with no severe adverse events. Lessons: The present case demonstrates that HSCT including PBSCT might be an effective new therapeutic option for refractory intestinal BD with MDS when immunosuppressive therapy has achieved insufficient efficacy.

Thoracic aortic aneurysms and dissections (TAAD) are rare in children and often associated with underlying genetic disorders accompanied with other systemic manifestations, including connective or osteo-articular tissue diseases.We report the case of a 10-year-old girl with a novel nonsense SMAD3 mutation, p.Glu102X, who presented with familial TAAD without any signs of osteoarthritis. Histological analysis of aorta fragments from the patient with TAAD obtained during surgery revealed elastin degradation and inflammatory infiltration of T cells with dense CD31 + microvessels, which is consistent with previous findings. Interestingly, the family members with the SMAD3 mutation developed IgA nephropathy.Because the TGF-β/Smad signalling pathway plays an important role in the primary pathogenesis of IgA nephropathy and TAAD, we presume that IgA nephropathy could be a novel clinical phenotype of SMAD3 deficiency. Further accumulation of genetically proven cases with SMAD3 deficiency is needed to more accurately characterize phenotypic variability and elucidate a wide spectrum of TGF-β-associated disorders.

A 40-year-old man with a history of oral and ileocecal ulcers, acneiform lesions, erythema nodosum and deep vein thrombosis presented with fever, abdominal pain and a pulsatile mass in the right groin. Two months prior to the presentation, he underwent stent grafting via the right femoral artery for an abdominal aortic aneurysm. Enhanced computed tomography disclosed aneurysms at the both ends of the stent (blue and green arrows in the panels A and B) and at the right femoral puncture site (blue arrowhead). This article is protected by copyright. All rights reserved.

BACKGROUND: Alkaptonuria, caused by a deficiency of homogentisate 1,2-dioxygenase, results in the accumulation of homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) in the urine. Alkaptonuria is suspected when the urine changes color after it is left to stand at room temperature for several hours to days; oxidation of homogentisic acid to benzoquinone acetic acid underlies this color change, which is accelerated by the addition of alkali. In an attempt to develop a facile screening test for alkaptonuria, we added alkali to urine samples obtained from patients with alkaptonuria and measured the absorbance spectra in the visible light region. METHODS: We evaluated the characteristics of the absorption spectra of urine samples obtained from patients with alkaptonuria (n = 2) and compared them with those of urine specimens obtained from healthy volunteers (n = 5) and patients with phenylketonuria (n = 3), and also of synthetic homogentisic acid solution after alkalization. Alkalization of the urine samples and HGA solution was carried out by the addition of NaOH, KOH or NH4OH. The sample solutions were incubated at room temperature for 1 min, followed by measurement of the absorption spectra. RESULTS: Addition of alkali to alkaptonuric urine yielded characteristic absorption peaks at 406 nm and 430 nm; an identical result was obtained from HGA solution after alkalization. The absorbance values at both 406 nm and 430 nm increased in a time-dependent manner. In addition, the absorbance values at these peaks were greater in strongly alkaline samples (NaOH- KOH-added) as compared with those in weakly alkaline samples (NH4OH-added). In addition, the peaks disappeared following the addition of ascorbic acid to the samples. CONCLUSIONS: We found two characteristic peaks at 406 nm and 430 nm in both alkaptonuric urine and HGA solution after alkalization. This new quick and easy method may pave the way for the development of an easy method for the diagnosis of alkaptonuria.