Effectiveness and safety of plasma exchange for anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease refractory to intensive immune suppression therapy: A case series.

INTRODUCTION: Clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with rapidly progressive interstitial lung disease (RP-ILD) is often refractory for intensive immunosuppression. In this study, we verified the effectiveness and safety of plasma exchange (PEx) for this lethal disease. METHODS: We retrospectively examined the clinical course and adverse effect (AE) of 12 patients with anti-MDA5 Ab-positive CADM between January 2017 and December 2021 in our hospital. RESULTS: Five out of six patients treated with simple PEx using fresh frozen plasma or 5% albumin survived with or without home oxygen therapy. Multiple PEx (15-20 times) were required to achieve satisfactory improvement as well as remission of CADM. The AEs caused by PEx were resolved using conventional methods. CONCLUSION: PEx might be a promising option for controlling the disease activity of anti-MDA5 Ab-positive CADM with severe RP-ILD and may contribute to better survival.

Nephrotic "full-house" glomerulonephritis successfully treated with antibiotics alone in secondary syphilis: a case report.

A Japanese female in her twenties developed general edema with heavy proteinuria, and was referred to our hospital. She exhibited the common clinical manifestation of idiopathic nephrotic syndrome with massive proteinuria (20.37 g/day), hypoalbuminemia (1.8 g/dL), and hypercholesterolemia (300 mg/dL). Routine admission tests were positive results for both the rapid plasma reagin latex agglutination test for syphilis (RPR) and the Treponema pallidum particle agglutination assay (TPHA). As such, we made her a diagnosis of nephrotic syndrome due to secondary syphilis. Renal biopsy revealed "full-house" nephropathy. Following the commencement of penicillin treatment, she developed skin rash, indicating the Jarisch-Herxheimer reaction (JHR). Her nephrotic syndrome responded rapidly and she achieved complete remission with antibiotic therapy alone after 4 weeks. In light of the increasing incidence of syphilis in Japan, clinicians should consider syphilis as a reversible cause of nephrotic syndrome.

Primary Myelofibrosis-Related Renal Disorders Treated with a Janus Kinase Inhibitor.

Extramedullary hematopoiesis is widely known to occur in patients with primary myelofibrosis (PMF). Autopsy studies on individuals with PMF revealed that extramedullary hematopoiesis occurred in the kidneys in 35% of the cases, but there is little awareness regarding such lesions. A 63-year-old man was diagnosed with PMF based on a detailed examination of persistent high white blood cells. An examination of the patient's medical records revealed an increased white blood cell count, deterioration of kidney function, and urinary protein excretion developed simultaneously. Thus, a kidney biopsy was performed. Advanced lymphocyte invasion was recognized in the interstitial tissue, and the tubular structure was highly disrupted. Based on these findings, he was diagnosed with interstitial nephritis. However, because of the large number of cells with nuclear atypia in the stroma, additional immunohistochemical staining was also performed, such as glycophorin A, naphthol AS-D, myeloperoxidase, and CD42b. As a result, invasion of three lineages of immature cells, erythroblasts, megakaryocytes, and granulocytes, was identified. Renal dysfunction resulting from interstitial cellular infiltration due to extramedullary hematopoiesis was therefore diagnosed. Treatment with ruxolitinib was initiated after a renal biopsy and the rate of decline in renal function was slightly reduced. Although, in myeloproliferative disorders, proliferative glomerular lesions are widely considered to be renal disorders, there is little awareness regarding interstitial lesions. Extramedullary hematopoiesis of the kidney in PMF is not uncommon, but 40% of cases are reportedly misdiagnosed as interstitial nephritis. Because extramedullary hematopoiesis can be controlled by ruxolitinib, early detection is important.

Autoimmune Factor V Deficiency That Took 16 Years to Diagnose due to Pseudodeficiency of Multiple Coagulation Factors.

A 70-year-old man presented to our hospital with intramuscular hemorrhage in the right thigh. He had exhibited a tendency to bleed for the last 16 years and had visited several medical institutions, but no diagnosis had been made. Since the risk of sudden bleeding was assumed to be high due to his age, we decided to examine him in our department. A coagulation abnormality with prothrombin time-international normalized ratio (PT-INR) of 4.5 and activated partial thromboplastin time (aPTT) of 99.6 seconds was observed, but the platelet count, fibrinogen, and PIVKAII were within normal limits. Coagulation activities of factor V, VII, VIII, IX, X, XI, XII, and XIII were all reduced. Anti-factor VIII and IX antibodies which were measured by the Bethesda method, lupus anti-coagulant (diluted Russell snake venom time method) and anti-cardiolipin antibody were also positive. The results of these tests were comparable to those undertaken 15 years ago when they were scrutinized at the university hospital. We suspected the presence of anti-factor V antibodies because there was a dissociation between the thrombotest values measured and those calculated from the PT-INR. Moreover, cross-mixing test showed an immediate inhibitor pattern. Subsequently, factor V antibodies were confirmed by the immunoblot method and the diagnosis of autoimmune factor V deficiency was made. When factor V, which is downstream of the coagulation cascade, is inhibited, coagulation test using the one-stage clotting method shows a pseudolow value. Therefore, extensive abnormalities of coagulation factor activity and inhibitor assay should be interpreted with caution, and the presence of a high titer of factor V inhibitor should be considered.

Quetiapine-induced thrombotic microangiopathy in a patient on maintenance dialysis.

Quetiapine has been reported to cause immune-mediated thrombotic microangiopathy (TMA), although few cases have been reported thus far. A 71-year-old man with autosomal dominant polycystic kidney disease on maintenance dialysis was hospitalized with a hemorrhagic basal ganglia stroke, and was treated with 25 mg quetiapine for delirium from day 4 of admission. There was no worsening of consciousness, fever, diarrhea, or elevated blood pressure during the hospitalization. Gingival bleeding appeared on day 35, and the platelet count on day 38 was 0.5 × 104/µL (13.2 × 104/µL on day 16). The presence of 1% schistocytes, high LDH level, inability to measure haptoglobin, negative direct Coombs test, and normal prothrombin time and activated partial thromboplastin time indicated TMA. We considered an exclusionary diagnosis of drug-induced TMA, because of normal ADAMTS13 activity, no evidence of complement activation and the absence of Shiga toxin or symptoms of collagen disease or cancer. Quetiapine was the most likely causative factor; however, all drugs, including heparin, were discontinued or changed. Due to persistent microbleeding, platelet transfusions were performed several times. After only quetiapine was discontinued, the platelet count recovered smoothly to 3.1 and 7.2 × 104/µL on days 45 and 72, respectively; LDH and fibrinogen levels normalized on day 47. All medications, except quetiapine, were restarted sequentially after day 47, without subsequent thrombocytopenia. Platelet activation predominantly by a drug-dependent antibody might be the etiology of quetiapine-induced TMA. Plasmapheresis may not be necessary for quetiapine, because of its unproven efficacy in drug-induced TMA.

Ascites management by cell-free concentrated ascites reinfusion therapy during recovery from drug-induced acute liver injury: a case report.

BACKGROUND: The symptoms of drug-induced hepatic injury are manifold; however, the presence of ascites indicates a severe disease condition. The rapid accumulation of ascites is distressing and requires palliative treatment. Because many cases are addressed by repeated large-volume paracentesis, often resulting in impairment due to protein and electrolyte loss, a different approach is required. CASE PRESENTATION: A 61-year-old Japanese man on maintenance dialysis was admitted to our hospital with acute liver injury. Our patient was diagnosed as having drug-induced liver injury due to warfarin or diltiazem, which started immediately after coronary artery bypass grafting 7 months previously. One month after admission, our patient's hepatic encephalopathy remained grade 1 and his prothrombin time international normalized ratio was maintained at < 1.5. However, the liver was markedly atrophied with massive ascites. Although liver transplantation was desired, he was considered unfit for transplantation because of his renal and cardiac complications. Therefore, we devised a strategy to manage the massive ascites with cell-free concentrated ascites reinfusion therapy while awaiting liver regeneration. At first, cell-free concentrated ascites reinfusion therapy was required frequently because ascites accumulated rapidly. But the fluid retention interval was gradually extended as intended, and cell-free concentrated ascites reinfusion therapy was withdrawn after 8 months. During that time, the size of his liver increased from 1419 cm3 to 1587 cm3 on computed tomography. CONCLUSIONS: Cell-free concentrated ascites reinfusion therapy is an apheresis therapy in which ascites are collected aseptically by paracentesis, concentrated, and then reinfused intravenously. This treatment has the advantage of preserving nutrition by reusing the fluid. Previously, cell-free concentrated ascites reinfusion therapy was used only for the management of ascites in patients with cirrhosis or carcinomatous peritonitis. This case suggests that palliation and maintenance of nutritional status with cell-free concentrated ascites reinfusion therapy may be useful as an adjunct to liver regeneration in drug-induced hepatic injury.

Azathioprine Hypersensitivity Syndrome during Treatment of Severe Interstitial Lung Disease with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Azathioprine is used to treat anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitis. Azathioprine hypersensitivity syndrome is often missed. An 81-year-old man undergoing treatment for interstitial pneumonia developed a high fever and was diagnosed with ANCA-associated vasculitis based on an elevated myeloperoxidase- (MPO-) ANCA titer and renal biopsy findings. After induction therapy, his clinical symptoms improved, but his MPO-ANCA remained elevated (>300 U·L-1) and hematuria persisted. Prednisolone plus azathioprine was administered as maintenance therapy. Three exacerbations of the inflammatory response occurred during the subsequent 3 months. In each instance, we suspected opportunistic infection or a flare-up of vasculitis. The first exacerbation was treated with an increased prednisolone dose and antibiotics. At the onset of the second exacerbation, which was accompanied by systemic erythema, we stopped azathioprine and administered antibiotics. The third exacerbation, which occurred the day after restarting azathioprine, involved a fever with chills and an acute inflammatory reaction; we therefore suspected an azathioprine allergy. A drug provocation test was performed, and a hyperinflammatory response was observed. The patient received prednisolone (15 mg·day-1) monotherapy; no further fever was observed during the subsequent 2 months. We therefore diagnosed azathioprine hypersensitivity syndrome. Under treatment with prednisolone (5 mg·day-1) and mycophenolate mofetil (1 g·day-1) (replacing the azathioprine), no signs of relapse or infection have occurred for more than two years. Renal function and the pulmonary lesions are stable, although the high MPO-ANCA titer and hematuria persist. The diagnosis of azathioprine hypersensitivity is often delayed because of the difficulty in identifying the relationship between immunosuppressive agents and hypersensitivity and in distinguishing this from infection or relapse of the primary disease. The misdiagnosis of azathioprine hypersensitivity leads to unnecessary treatment; thus, clinicians should consider allergic reactions specific to azathioprine when switching from induction to maintenance therapy.

Fibrillary Glomerulopathy with a High Level of Myeloperoxidase-ANCA: A Case Report.

An elderly woman was admitted with the chief complaint of gross hematuria. Laboratory values indicated a high myeloperoxidase-ANCA level. In renal histological examination, 40% of the glomeruli showed crescent formation, but immunofluorescence staining showed positivity for IgG, C3, and C1q. Furthermore, the deposition of fibrils in the glomerulus was noted on electron microscopy, and immunohistochemical staining showed strong positivity for DNA-J heat shock protein family member B9 (DNAJB9). Crescent formation is a common feature of fibrillary glomerulonephritis (FGN). Thus, in ANCA-positive crescentic glomerulonephritis, immunohistochemical assessments for immunoglobulins and DNAJB9, as well as electron microscopy, are important to correctly diagnose FGN.