Long-term prognosis of monoclonal immunoglobulin-associated glomerular diseases with non-organized deposits: A report of 38 cases from a Japanese single center.

Monoclonal immunoglobulin (MIg)-associated glomerular diseases with non-organized deposits are rare disorders. They have recently been categorized into light chain deposit disease (LCDD), light and heavy chain deposit disease (LHCDD), heavy chain deposit disease (HCDD), proliferative glomerulonephritis with MIg deposits (PGNMID) and its light chain only variant (PGNMID-LC), and membranous glomerulopathy with light chain-restricted deposits (MG-LC). In our Japanese cohort of more than 9,500 patients who underwent renal biopsy (1979 - 2020), we evaluated clinicopathological features and long-term outcomes in 38 patients with MIg-associated glomerular diseases with non-organized deposits: LCDD (n = 9), LHCDD (n = 8), HCDD (n = 5), PGNMID-membranoproliferative glomerulonephritis (MPGN) (n = 7), PGNMID-LC (n = 2), and MG-LC (n = 7). In patients with LCDD, a low estimated glomerular filtration rate (eGFR) at biopsy, a high detection rate of urinary MIgs, a high incidence rate of multiple myeloma, and sever tubulointerstitial and vascular lesions were significant clinicopathological characteristics. Median duration of follow-up in each group was 42 - 114 months. Most patients were treated with steroid-based therapy. Patients with LCDD, LHCDD, HCDD, and MG-LC were recently treated with bortezomib-based therapy. Renal survival rate was significantly shorter for LCDD than of PGNMID and MG-LC. Patient survival rate was significantly longer for MG-LC than HCDD and PGNMID. Major causes of death were pulmonary and cardiovascular complications. Among disease groups, significant differences were observed in eGFR at biopsy, detection rates of urinary MIgs, incidence rates of multiple myeloma, severities of tubulointerstitial and vascular lesions, and long-term outcomes.

Evaluation of a newly proposed renal risk score for Japanese patients with ANCA-associated glomerulonephritis.

BACKGROUND: We determined the usefulness and prognostic ability of the renal risk score (RRS), proposed in Europe, for Japanese patients with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) and high myeloperoxidase (MPO)-ANCA positivity; these aspects remain to be verified. METHODS: This retrospective study was conducted on 86 Japanese patients with new, biopsy-confirmed AAGN. We calculated the RRS and analyzed the relationship between this classification, and clinicopathological features and prognosis. We also compared the predictive values between RRS for endpoints including renal death and conventional prognostic tools for patients with AAGN. RESULTS: There were 33, 37, and 16 patients in the low-, medium-, and high-risk groups, respectively. All patients were MPO-ANCA positive. The median follow-up period was 33 months; 16 (18.6%) patients progressed to end-stage renal disease (ESRD). In the high-risk group, 9/16 (56.3%) patients progressed to ESRD, and renal prognosis was significantly poorer than that in other groups (low-risk group, P < 0.001; medium-risk group, P = 0.004). In Cox multivariate regression analysis, RRS was an independent, poor renal prognostic factor (hazard ratio 5.22; 95% confidence interval 2.20-12.40; P < 0.001). The receiver-operating characteristic curves of the RRS for each endpoint were comparable with those of the 2010 histological classification and those of the severity classification of Japanese rapidly progressive glomerulonephritis. CONCLUSIONS: This is the first study to report the usefulness of the RRS for predicting renal outcomes among Japanese patients with AAGN. Our predictive value of the RRS was comparable with that of conventional prognostic tools.

[Postmortem diagnosis of intravascular large B-cell lymphoma after atraumatic splenic rupture due to splenic infiltration].

Atraumatic splenic rupture (ASR) is a rare but fatal complication of malignant lymphoma. However, only one case of intravascular large B-cell lymphoma (IVLBCL)-related ASR (IVLBCL-ASR) has previously been reported, and the mechanism of IVLBCL-ASR is unknown. We present the case of a 78-year-old man who died unexpectedly and was diagnosed with IVLBCL-ASR pathologically by autopsy. A massive intraperitoneal hemorrhage and four lacerations on the splenic surface were discovered during the autopsy. CD20-positive lymphoma cells that infiltrated into small vessels were highly concentrated in the center of the spleen and were only slightly distributed in the lacerations on the splenic surface. Therefore, increased intrasplenic pressure due to lymphoma cell proliferation was identified as the cause of ASR. The patient had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for tongue cancer evaluation 3 months earlier, and positive uptake was found in the right adrenal gland, where lymphoma cell infiltration was confirmed by the autopsy. Our findings suggest that clinicians should be aware that the advanced stage of IVLBCL can cause fatal ASR via increased intrasplenic pressure. Therefore, early diagnosis and early treatment intervention are desirable to prevent the onset of IVLBCL-ASR, and 18F-FDG PET/CT is useful for the early diagnosis of IVLBCL.

Early Pulmonary Rehabilitation with Neuromuscular Electrical Stimulation in a Patient with Acute Exacerbation of Rheumatoid Arthritis-associated Interstitial Lung Disease: A Case Report.

INTRODUCTION: Early implementation of neuromuscular electrical stimulation (NMES) has been reported to prevent muscle atrophy and physical functional decline in patients requiring mechanical ventilation. However, its effect in patients with acute exacerbation of interstitial lung disease (ILD) remains unclear. We herein report our experience using the NMES combined with mobilization in a patient with an acute exacerbation of rheumatoid arthritis-associated ILD (RA-ILD) requiring mechanical ventilation. CASE PRESENTATION: A 74-year-old man was admitted to the intensive care unit (ICU) and put on mechanical ventilation due to severe acute exacerbation of RA-ILD. Early mobilization and the NMES using a belt electrode skeletal muscle electrical stimulation system were started on day 7 of hospitalization (day 2 of ICU admission). The NMES duration was 20 min, performed once daily. The patient could perform mobility exercises on day 8 and could walk on day 16. We assessed his rectus femoris and quadriceps muscle thicknesses using ultrasound imaging, and found decreases of 4.5% and 8.4%, respectively, by day 14. On day 27, he could independently visit the lavatory, and the NMES was discontinued. He was instructed to start long-term oxygen therapy on day 49 and was discharged on day 63. His 6-minute walk distance was 308 m and his muscle thickness recovered to levels comparable to those at the initial evaluation at the time of discharge. CONCLUSION: Combining the NMES and mobilization started in the early phase and continued after ICU discharge was safe and effective in a patient with a severe acute exacerbation of RA-ILD.

Reduced Rate of Disease Flares in Japanese Patients with Systemic Lupus Erythematosus: An Altered Balance between the Use of Glucocorticoids and Immunosuppressants in Recent Decades.

Objective This study examined whether or not the disease control in Japanese patients with systemic lupus erythematosus (SLE) had improved in recent years and its possible association with altered balance between the use of glucocorticoids and immunosuppressants. Methods We enrolled Japanese patients with SLE who visited our medical center during 2013-2017 (Group A, 75 patients) and compared them with patients encountered during 1999-2003 (Group B, 69 patients; not overlapping with Group A). Patient background characteristics, doses of glucocorticoids, and the use of immunosuppressants at the times of SLE onset and disease flares were reviewed from the medical records. Disease flare was defined as new British Isles Lupus Assessment Group 2004 A or B scores in at least one system. Results Lupus nephritis and neuropsychiatric manifestations were less frequently observed in Group A than in Group B (p=0.042 and p=0.045, respectively). Although the initial glucocorticoid dosage was similar between the groups, the inclusion rate of immunosuppressants in the initial SLE treatment was significantly higher in Group A than in Group B (56% vs. 6% in Group B, p<0.001). The median number of SLE flares per person-year was significantly lower in Group A than in Group B (0 vs. 0.3, respectively, p<0.001), and a propensity score-matched analysis indicated the association of SLE flare with the non-use of immunosuppressants in the initial treatment (p=0.012). The rates of infectious diseases and other complications were similar between the groups. Conclusion The recent aggressive use of immunosuppressants in Japan resulted in a reduction in the rate of SLE flare.

Performance of the Revised Classification Criteria for Systemic Autoimmune Rheumatic Diseases and Their Overlap Syndromes.

Objective We evaluated the performance of the revised classification criteria for assessing different systemic autoimmune rheumatic diseases and their overlap syndromes. Methods A total of 652 patients with or highly suspected of having systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM) or rheumatoid arthritis (RA) were included in this study. The 1997 revised American College of Rheumatology (ACR) and the 2019 European League Against Rheumatism (EULAR)/ACR criteria for SLE, the 1980 ACR and the 2013 ACR/EULAR criteria for SSc, the criteria by Bohan and Peter and the 2017 EULAR/ACR criteria for PM/DM, and the 1987 revised ACR and 2011 ACR/EULAR criteria for RA were used for disease classification. Results The old and new criteria and a clinical diagnosis were used to respectively classify 103, 106 and 105 SLE patients; 35, 47 and 58 SSc patients; 18, 23 and 33 PM/DM patients; and 297, 389 and 468 RA patients. Sensitivity increased from 82.9% to 92.4% in SLE, from 56.9% to 79.3% in SSc, from 54.5% to 66.7% in PM/DM, and from 62.6% to 80.8% in RA. SLE-SSc was the predominant type of clinical overlap syndrome, while SLE-RA was the most classifiable. Conclusion The revised classification criteria for all the diseases showed an improved sensitivity, and SLE-overlap syndrome was predominant, regardless of the criteria sets.

Adult-onset Still's Disease during Pregnancy Treated with Tocilizumab.

A 28-year-old woman exhibited a spiking fever, arthritis, and liver disfunction when she was 22 weeks pregnant. She was diagnosed with adult-onset Still's disease (AOSD). As her condition was resistant to corticosteroid therapy, tocilizumab (TCZ) was selected. The TCZ treatment was effective, and she delivered a healthy child while receiving TCZ treatment. Cases in which AOSD first arises during pregnancy are rare, and there have been no reports of TCZ treatment for AOSD being initiated during pregnancy. Although the safety of TCZ treatment during pregnancy has not been established, it may be effective against severe AOSD that develops during pregnancy.

Finger Joint Cartilage Evaluated by Semiquantitative Ultrasound Score in Patients With Rheumatoid Arthritis.

OBJECTIVE: Joint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. Since joint space narrowing (JSN) is not a direct evaluation of cartilage using radiography, we aimed to examine the validity of ultrasound (US) cartilage evaluation using a semiquantitative method in patients with RA. METHODS: We enrolled 103 patients with RA who were in remission or showing low disease activity and 42 healthy subjects. The cartilage thickness of the bilateral metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the second to fifth fingers was measured by US, and the recorded images were scored semiquantitatively using a scale of 0-2. In addition, the JSN of the corresponding joints was scored using a hand radiograph. The relationships between total cartilage thickness, its semiquantitative score, and JSN score were assessed using Spearman's rank correlation coefficients. RESULTS: Total cartilage thickness was significantly thinner in patients with RA compared to healthy subjects for both the MCP and PIP joints (both P < 0.001). The semiquantitative sum of 16 joints ranged from 2 to 26 (median 8) in patients with RA, which was significantly greater than the 0-11 (median 4) in healthy subjects (P < 0.001). In patients with RA, the semiquantitative score showed a significant negative correlation with cartilage thickness (ρ = -0.64, P < 0.001) and a significant positive correlation with JSN score (ρ = 0.66, P < 0.001). Furthermore, these scores showed a significant correlation with RA disease duration. CONCLUSION: A simplified and direct evaluation of finger joint cartilage damage by semiquantitative US score is valid and useful for patients with RA.

Successful Pregnancies in a Patient with Childhood-onset Steroid-dependent Nephrotic Syndrome during Rituximab Maintenance Therapy.

There are an increasing number of reports on the safe use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, in pregnant women with hematological malignancies or refractory autoimmune diseases. In 2014, the use of RTX for patients with complicated steroid-dependent nephrotic syndrome (SDNS) was approved in Japan. We herein report a woman with childhood-onset complicated SDNS due to focal and segmental glomerulosclerosis, who had two successful pregnancies while receiving RTX maintenance therapy. No adverse complications were observed during the pregnancies, and she delivered healthy newborns. This case suggested that RTX may be used safely in pregnant women complicated with SDNS.