Plasmapheresis for systemic vasculitis.

Systemic vasculitides include a variety of, and numerous diseases. In 2012, the International CHAPEL HILL Consensus Conference (CHCC2012) led to a major reorganization of the classification of vasculitis, and this is still in wide use today. Although the results of plasmapheresis for individual diseases have been sometimes shown, there are few systematic reviews that discuss the effects along with vasculitis classification. Therefore, we will discuss the efficacy and the latest evidence for each vasculitis according to the CHCC 2012 classification in this review. This review provides a comprehensive overview of the estimation of plasmapheresis in each of the vasculitides, with a particular focus on small vasculitides, which have recently discussed frequently. For some time now, plasma exchange therapy (PEX) has been frequently used and is expected to be effective in some diseases, most of which are included in small vessel vasculitides. In particular, data showing efficacy have been accumulated for immune complex vasculitis, and the recommendation seems to be high. For instance, anti-GBM nephritis, concomitant use of PEX is essential and strongly recommended. On the other hand, for ANCA-related vasculitis among small vessel vasculitis, RCTs have recently shown negative results. In particular, the PEXIVAS trial statistically showed that PEX has no potential to reduce the mortality and renal death in AAV, but the ASFA, ACR, and KDIGO guidelines following this trial all regard PEX as salvage therapy or selective treatment for severe cases. As plasmapheresis is often performed in combination with other therapies, it is difficult to evaluate to clarify its efficacy on its own, and this predisposition may be pronounced in vasculitis, a rare disease. Although statistically significant differences are not apparent, the diseases that show a trend toward efficacy may possibly include treatment-sensitive subgroups. Further analysis is expected in the future.

Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

Clinical features of psoriatic arthritis.

Psoriatic arthritis (PsA) is associated with decreased quality of life. As delayed diagnosis may lead to progressive joint destruction and long-term disability, the key clinical features of PsA should be recognizable to a wide range of clinicians to facilitate early diagnosis. In addition to assessment and identification of skin and nail lesions, which occur in up to 85% of those with musculoskeletal manifestations, clinicians should be aware of both the peripheral and axial manifestations of musculoskeletal disease reviewed here. Peripheral joint diseases include polyarticular, oligoarticular, distal, and arthritis mutilans subtypes, and cognizance of these patterns of disease, as well as periarticular manifestations, including dactylitis and enthesitis, is useful for swift diagnosis of PsA. Axial psoriatic arthritis (axial PsA), also known as the spondylitis subtype, may be limited to the spine and sacroiliac joints, but may also affect peripheral structures. Meticulous history-taking and physical examination and familiarity with appropriate imaging studies are often necessary to distinguish axial-PsA from other differential diagnoses. Swift diagnosis and treatment are necessary to both control PsA disease and mitigate the risks of the many associate comorbidities that may accompany it.

Extensive bilateral renal metastases of non-small cell lung carcinoma caused acute kidney injury resulting in end-stage renal disease.

Non-small cell lung carcinoma unusually causes clinically relevant metastases in the kidney while they are usually found only in autopsy. Acute kidney injury (AKI) due to direct metastatic invasion of a solid tumor is also very rare whereas it usually happens with hematologic malignancy, including lymphoma. We report a case with these two rarities. A 54-year-old man who had a 6.7 × 6.0 cm-sized tumor in the left upper lobe of the lung in computed tomography was diagnosed as squamous cell lung carcinoma with bronchoscopy with biopsy. His renal function was normal and no proteinuria or hematuria was recognized. He underwent left upper lobectomy and the pathologic examination revealed pT4N1M0 stage IIIA disease. Four months after the surgery, a single brain metastasis in the right frontal lobe found in brain magnetic resonance imaging was treated with Gamma Knife radiosurgery. He presented with macroscopic hematuria and AKI (the serum creatinine level was 1.35 mg/dL) nine months after surgery. The cause was enormous bilateral renal metastases, maximally 8 cm-sized lesions with poor enhancement, which were found in enlarged bilateral kidneys in enhanced CT. Intrapulmonary metastatic lesions were also newly detected. Chemotherapy with pembrolizumab, an antibody against anti-programmed cell death protein 1, had little effect and his renal function continued to decline rapidly, resulting in end-stage renal disease and maintenance hemodialysis. Chemotherapy with carboplatin and paclitaxel was additionally performed. However, two months after hemodialysis induction, the patient died with pneumonia and acute respiratory distress syndrome.

Long-term efficacy of early infliximab-induced remission for refractory uveoretinitis associated with Behçet's disease.

BACKGROUND: To evaluate long-term efficacy of infliximab (IFX) in refractory uveoretinitis associated with Behçet's disease (BD) depending on uveoretinitis duration. METHODS: Records of 16 patients with BD (32 eyes) followed for >5 years after starting IFX, were retrospectively reviewed. Long-term efficacy was compared between patients with short duration (≤18 months, n=7) versus long duration (>18 months, n=9) of their uveoretinitis prior to starting IFX. RESULTS: The median follow-up after starting IFX was 132 months (76-146 months). Mean frequency of attacks and the 1-year Behçet's Disease Ocular Attack Score 24 decreased significantly over 10 years. Overall, the percentage of eyes with a best-corrected visual acuity (BCVA) ≥1.0 increased from 47% at baseline to 59% at 5 years; the percentage of eyes with a BCVA ≤0.1 was 19% at both baseline and 5 years. The frequency of ocular attacks decreased similarly in both short duration and long duration groups; however, the percentage of eyes with a BCVA ≥1.0 at 5 years was 100% in the short duration group versus 28% in the long duration group. IFX was discontinued in four patients with an excellent response to IFX therapy; all were young male patients in the short duration group with good BCVA bilaterally, and none had inflammatory recurrences over a median follow-up of 56 months off IFX. CONCLUSION: Initiation of IFX therapy in patients with BD within 18 months of their uveoretinitis onset was more effective in maintaining good BCVA than after 18 months.

Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

BACKGROUND: The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. CONCLUSION: On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Adult-onset Still's disease-like manifestation accompanied by the cancer recurrence after long-term resting state.

A 72-year-old woman presented 9 months ago with skin rash on her bilateral forearms, which was followed by intermittent high fever, and stiffness and swelling of her bilateral fingers. She was diagnosed with seronegative rheumatoid arthritis (RA). She had a past history of breast cancer and had undergone breast preservation surgery 13 years previously. During admission in our hospital, she developed high fever and leukocytosis with a relapsing skin rash, sore throat, polyarthralgia and increased levels of serum ALT/AST and ferritin, all of which fulfilled Yamaguchi's criteria for adult-onset Still's disease (AOSD). While we tried to exclude other diseases that may show AOSD-like manifestations, pancytopenia rapidly developed and bone marrow biopsy strongly suggested the diagnosis of macrophage activating syndrome (MAS). Accordingly, steroid pulse therapy was begun, followed by oral glucocorticoid therapy. Thereafter, all of her symptoms improved, but systemic rash, inflammatory signs and pancytopenia gradually progressed. The results of bone marrow pathology, which returned 2 weeks after the beginning of treatment, revealed hemophagocytosis with CK7-positive/CK20-negative atypical cells that suggested recurrence of breast cancer in the bone marrow, thus all of her AOSD-like symptoms were considered to be paraneoplastic manifestations of late-onset metastatic breast cancer. She was treated successfully with chemotherapy. When we see the patients showing AOSD-like symptoms with a history of malignancy, we should consider the possibility of paraneoplastic syndrome due to cancer recurrence.

Tenosynovitis with Rice Body Formation Due to Mycobacterium Intracellulare Infection After Initiation of Infliximab Therapy.

BACKGROUND Rheumatoid arthritis tenosynovitis is difficult to discriminate from non-tuberculous tenosynovitis on the basis of radiological and pathological findings. CASE REPORT A 74-year-old woman with a 4-year history of rheumatoid arthritis was referred to our hospital to undergo treatment for uncontrollable tenderness and swelling in her right third metacarpophalangeal joint, right wrist, and left knee joint. In the previous year, she underwent surgery at a local hospital for the swelling in her right metacarpophalangeal joint, the information of which was not known precisely, but the swelling subsided in due course after an operation. We treated the patient with infliximab (monthly intravenous infusions of 150 mg), but 2 months later, she complained of exacerbation of the swelling in her right third metacarpophalangeal joint and right wrist, and fluid discharge that contained Mycobacterium intracellulare. After synovectomy and aggressive debridement in the palmar side of the right wrist, she was diagnosed as having granulomatous tenosynovitis caused by the M. intracellulare infection and abundant rice body formation in the right carpal tunnel area. We considered the rice bodies inside and outside the bursa, along with a history of tenosynovitis exacerbation after initiation of infliximab therapy (tumor necrosis factor alpha inhibitor [TNFi]), to be related to the M. intracellular infection. CONCLUSIONS Tenosynovitis caused by atypical mycobacteria is uncommon and usually affects the hand or wrist. Therefore, for early diagnosis, mycobacterial infection should be considered in cases of indolent chronic granulomatous tenosynovitis, especially in RA cases that recur after TNFi therapy is started.

Multiple aortic aneurysms complicated by a rupture in the systemic lupus erythematosus: a case report.

We report the case of a 61-year-old female who suffered from systemic lupus erythematosus (SLE) and died of a ruptured abdominal aortic aneurysm (AA). She was diagnosed to have SLE at 39 years of age, and was administrated steroids and prostaglandin E(2). From 52 years of age, AA, peripheral arterial occlusion, and multiple organ infarctions appeared repeatedly. At 59 years of age, she was found to be affected by antiphospholipid antibody syndrome (APS). In the following year, expansion of an abdominal AA was identified, but she was given only conservative treatment. In the next year, sudden epigastralgia and dyspnea occurred, and she died. An autopsy revealed multiple AAs up to 11 cm in diameter, one of which showed ruptures, forming a retroperitoneal hematoma. Marked atherosclerosis of the aorta was noted, and she also had aortic dissection accompanied by cystic medial necrosis (CMN). An old myocardial infarction and brain infarction were also confirmed. Although SLE with APS is common, a complication of the disease by CMN, multiple AAs, or ruptured AA has been described in several cases to date. Regarding the etiology of this complicated presentation, we presume synergistic involvement of various factors, such as atherosclerosis and CMN associated with SLE, thrombosis due to APS, and prolonged steroid therapy.

Alteration of redox state of human serum albumin before and after hemodialysis.

BACKGROUND: Persistent hypoalbuminemia is a predictor of death in long-term maintenance hemodialysis patients, although cardiovascular diseases remain the leading cause of death. A decreased serum antioxidant activity in maintenance hemodialysis patients may contribute to increased oxidative damage, and may be associated with accelerated atherosclerotic changes. METHODS: The aim of this study was to examine the redox state of human serum albumin in maintenance hemodialysis patients by high-performance liquid chromatography (HPLC) using a fluorescence detector. RESULTS: HPLC of human serum albumin on a Shodex-Asahipak ES-502N column at pH 4.85 showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are the reduced and oxidized forms of human serum albumin, respectively. The mean +/- SD percentage of the HMA fraction of human serum albumin was significantly lower in maintenance hemodialysis patients than in age-matched normal subjects. The percentage of HMA increased 3-5 h after starting the hemodialysis and then decreased to subnormal levels. CONCLUSION: This suggests that serum albumin may be a major extracellular antioxidant in maintenance hemodialysis patients, and that hemodialysis may rescue serum albumin reduction by inducing intermolecular sulfhydryl-disulfide exchange reaction.

[Secondary nephrotic syndrome due to collagen disease and vasculitis].

The most frequent and representative nephrotic syndrome associated with collagen disease is encountered in patients suffering from lupus nephritis. Lupus nephritis is a glomerulonephritis, which discloses various localizations of immune complexes in the endothelium, mesangium and subepithelium. In addition, vasculitides complicated by nephrotic syndrome also show the deposition of immune complexes in their glomeruli, such as Henoch-Schönlein nephritis and cryoglobulinemic nephritis. The pathogenetic mechanisms of these nephrotic syndromes are explained as follows. The depositions of immune complexes in glomeruli causes proteinuria through a variety of mechanisms. Namely, subendothelial and mesangial immune deposits give capillary and mesangial injuries as well as inflammation that are mediated through activation of complements and cytokines, and subsequently leads to nephrotic-range proteinuria and impairment of renal function. On the other hand, subepithelial and intramembranous deposits disrupt the regulated arrangement of epithelial cells and slit diaphragms, and then disturb the slit diaphragms. The eventual dysfunction of slit diaphragms accordingly progresses to massive proteinuria even without capillary injury. Therefore, nephrotic syndrome associated with collagen disease or vasculitis is usually observed in lupus nephritis or vasculitis related to immune complex depositions, but is not observed in non-immune complex glomerulopathy or vasculopathy.

Efficient isolation of cDNA clones encoding rheumatoid arthritis autoantigens by lambda phage surface display.

Bacteriophage lambda surface display was used to isolate cDNA clones encoding autoantigens recognized by synovial fluid (SF) or sera from patients with rheumatoid arthritis (RA). We constructed cDNA libraries from human synovial sarcoma cells and synovial tissue, using the surface display vector lambdafoo. The cDNA libraries were screened by affinity selection using 40 SF and 44 sera as probes separately immobilized in microtiter wells. Phage clones isolated encode 13 different autoantigens; an unknown protein, two proteins previously unanalyzed as autoimmune antigens, three proteins previously unknown to be recognized by RA sera, and seven known RA antigens. When analyzed their sensitivity and specificity for RA by phage enzyme-linked immunosorbent assay, frequencies of sera that recognize the newly-isolated autoantigens ranged from 20.5 to 6.8% of a panel of RA sera, and 13.6-0% of other autoimmune disease sera. These results indicate that the lambda phage surface display may be powerful for the isolation of cDNA clones encoding autoantigens recognized by SF or sera from patients with not only RA but also other autoimmune diseases.