Efficacy of sutimlimab for cold agglutinin disease in a patient on chronic hemodialysis.

Reports of cold agglutinin disease (CAD), an autoimmune hemolytic anemia, in dialysis patients are limited. Recently, sutimlimab for CAD was covered by insurance. Herein, we report a case in which sutimlimab was effective in the treatment of CAD in a patient undergoing hemodialysis (HD). The patient was a 73 year-old Japanese man with an 11 year history of HD for diabetic nephropathy. He was admitted to our hospital for examination and treatment of erythropoiesis-stimulating agent (ESA)-induced hyporesponsive anemia and fatigue, which was present in the previous year October to March when temperatures were cooler. The patient was diagnosed with hemolytic anemia based on decreased hemoglobin levels, elevated reticulocyte count, elevated lactate dehydrogenase levels, and decreased haptoglobin levels. Furthermore, he was diagnosed with CAD based on a positive direct antiglobulin test for C3 and cold agglutinin tests. The patient did not respond well to an elevated dialysate temperature or rituximab therapy. After initiating sutimlimab treatment, an increase in the hemoglobin level was observed despite a decrease in temperature, and his fatigue disappeared. Anemia in hemodialysis patients is generally renal; however, some ESA resistance exists, which may be due to hemolytic anemia. In this case, the use of sutimlimab was effective in controlling hemolytic anemia due to CAD.

A Case of Macrophage Activation Syndrome With Elderly Onset Still's Disease Under Tocilizumab Treatment.

Adult-onset Still's disease in older adults is referred to as elderly onset Still's disease (EOSD). Few cases of tocilizumab (TCZ) use for EOSD management have been reported. Here, we report the case of an 87-year-old Japanese woman with EOSD who was not previously taking any medication. She had fatigue, sore throat, and loss of appetite for several days and gradually experienced difficulty walking. On examination, she was found to have a fever and erythema on the buttocks and extremities. Laboratory tests revealed leukocytosis with neutrophil predominance, elevated C-reactive protein (CRP) levels, and hyperferritinemia. A contrast-enhanced computed tomography scan of the chest to the abdomen showed no abnormalities. Antimicrobial therapy was initiated; however, the fever did not resolve. On day seven, 40 mg/day prednisolone (PDN) was started for EOSD in the absence of an obvious infection or a malignancy. On day 20, the fever recurred, and the patient was started on intravenous methylprednisolone (mPDN) half-pulse therapy (500 mg/day for three days). The fever resolved, and the CRP level decreased to 1 mg/dL but did not return to normal. On day 35, the fever recurred; therefore, 320 mg of TCZ was injected intravenously, and the PDN was tapered. On day 43, the patient tested positive for cytomegalovirus (CMV) antigenemia and improved on ganciclovir. On day 70, the patient developed fever, decreased white blood cell (WBC) and hemoglobin (Hb) levels, high lactate dehydrogenase (LDH) levels, hyperferritinemia, and elevated liver enzymes. Macrophage activation syndrome (MAS) was diagnosed due to hemophagocytosis on bone marrow examination. The patient was started on pulse therapy with glucocorticosteroids and cyclosporine. The patient's fever decreased, and her WBC count and LDH level normalized. The patient continued rehabilitation for muscle weakness due to prolonged hospitalization and high-dose steroid use and was discharged from the hospital on day 150. The findings in this case suggest that the use of TCZ during the remission induction phase of EOSD may lead to MAS.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. METHODS: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. RESULTS: Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary ß2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. CONCLUSION: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

A Lethal Combination: Legionnaires' Disease Complicated by Rhabdomyolysis, Acute Kidney Injury, and Non-Occlusive Mesenteric Ischemia.

BACKGROUND Legionnaires' disease is one of the most common types of community-acquired pneumonia. It can cause acute kidney injury and also occasionally become severe enough to require continuous renal replacement therapy (CRRT). Non-occlusive mesenteric ischemia (NOMI) is a condition characterized by ischemia and necrosis of the intestinal tract without organic obstruction of the mesenteric vessels and is known to have a high mortality rate. CASE REPORT A 72-year-old man with fatigue and dyspnea was diagnosed with Legionnaires' disease after a positive result in the Legionella urinary antigen test pneumonia confirmed by chest radiography and computed tomography. He developed acute kidney injury, with anuria, rhabdomyolysis, septic shock, respiratory failure, and metabolic acidosis. We initiated treatment with antibiotics, catecholamines, mechanical ventilation, CRRT, steroid therapy, and endotoxin absorption therapy in the Intensive Care Unit. Despite ongoing CRRT, metabolic acidosis did not improve. The patient was unresponsive to treatment and died 5 days after admission. The autopsy revealed myoglobin nephropathy, multiple organ failure, and NOMI. CONCLUSIONS We report a fatal case of Legionnaires' disease complicated by rhabdomyolysis, acute kidney injury, myoglobin cast nephropathy, and NOMI. Legionella pneumonia complicated by acute kidney injury is associated with a high mortality rate. In the present case, this may have been further exacerbated by the complication of NOMI. In our clinical practice, CRRT is a treatment option for septic shock complicated by acute kidney injury. Thus, it is crucial to suspect the presence of NOMI when persistent metabolic acidosis is observed, despite continuous CRRT treatment.

Eosinophilic Granulomatosis with Polyangiitis Presenting as Steroid-Responsive Sclerosing Cholangitis and Cholecystitis: A Rare Case Report.

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitic condition characterized by bronchial asthma and eosinophilia. While biliary involvement is uncommon in EGPA, we present a unique case of EGPA presenting as steroid-responsive sclerosing cholangitis and cholecystitis. This case highlights the importance of considering EGPA in the differential diagnosis of biliary diseases, especially in patients with a history of bronchial asthma. CASE REPORT A 47-year-old man with a history of bronchial asthma presented with fatigue, weight loss, and epigastralgia. Blood tests revealed eosinophilia and elevated inflammatory markers, leading to the diagnosis of EGPA. Further imaging studies, including magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography, confirmed the presence of sclerosing cholangitis and cholecystitis, a rare manifestation of EGPA. CONCLUSIONS Prompt treatment with prednisolone and azathioprine resulted in remission of symptoms and resolution of cholangitis and cholecystitis in this case. Our findings emphasize the importance of early recognition and appropriate management of EGPA-associated biliary involvement. Increased awareness of this rare manifestation may facilitate timely diagnosis and improve patient outcomes.

Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease.

OBJECTIVES: This study investigated the clinical features of IgG4-RKD patients with hypocomplementemia compared with those without it, so as to clarify the factors related to hypocomplementemia. METHODS: In this single-center retrospective study, we analyzed the clinical features of 25 patients with IgG4-RKD according to the presence/absence of hypocomplementemia. Additionally, we validated the results of a single-center study in a separate large multicenter cohort of 328 patients with IgG4-RD, and searched for factors related to hypocomplementemia. RESULTS: Serum IgG levels (p < .001), non-IgG4 IgG levels, calculated as the total IgG minus IgG4 (p < .001), serum IgG1 levels (p = .017), and the number of involved organs (p = .018) were significantly higher in the hypocomplementemia group. At relapse of renal lesions in four patients, all had serum IgG4 re-elevation, with the three with hypocomplementemia presenting worsening of hypocomplementemia and re-elevation of non-IgG4 IgG levels. In a validation cohort of 328 patients with IgG4-RD, multivariate logistic regression analysis indicated elevation of non-IgG4 IgG levels to be an independent factor related to hypocomplementemia in the patients with IgG4-RKD. CONCLUSION: The present study suggests that hypocomplementemia is associated with elevation of IgG subclasses other than IgG4 including IgG1 in IgG4-RKD.

Fulminant myocarditis and pulmonary cavity lesion induced by disseminated mucormycosis in a chronic hemodialysis patient: Report of an autopsied case.

Mucormycosis is a rare fungal infection occurring in the immunocompromised host. It is difficult to diagnose, and its cardiac involvement is extremely rare. Here, we report a 64-year-old Japanese man with a 5-year history of hemodialysis with disseminated mucormycosis causing fulminant myocarditis and pulmonary necrosis under glucocorticoid use. Two months before, he had received an implantable cardioverter defibrillator and started to take amiodarone for recurrent ventricular arrhythmias due to hypertensive cardiomyopathy. He developed amiodarone-induced interstitial pneumonia and then received glucocorticoid therapy. Although the interstitial pneumonia partially improved, a lung cavitary lesion developed in the upper right lobe. Antibiotics had no effect, and serologic tests, blood and sputum cultures and bronchoalveolar lavage fluid were all negative for infectious pathogens. Eventually, he died of fulminant myocarditis. Autopsy revealed disseminated mucormycosis with vascular invasion and fungal thrombi, hemorrhage and infarction in lung (cavity lesion), heart (severe myocarditis), brain, thyroid and subcutaneous tissue around the implantable cardioverter defibrillator. The lung cavitary lesion was the only clinical finding suggestive of mucormycosis before autopsy. When an immunocompromised patient shows a progressive lung cavity lesion, the possibility of mucormycosis should be considered so that a broad-spectrum antifungal agent can be empirically administered in a timely fashion.

Different factors underlie recurrent and de novo organ involvement in immunoglobulin G4-related disease.

OBJECTIVES: In IgG4-related disease (IgG4-RD), relapse including recurrent organ involvement (ROI) and de novo organ involvement (DNOI) occurs frequently during the clinical course. This study aimed to clarify the differences between the risk factors underlying ROI and DNOI in IgG4-RD. METHODS: We retrospectively investigated factors related to ROI and DNOI in 86 IgG4-RD patients. For assessment of factors related to ROI and DNOI, we performed uni- and multivariate Cox regression analyses. On stepwise multivariate analysis, we applied the variables with P < 0.1 in the univariate analysis and the predictors of relapse suggested in past reports. RESULTS: During the mean follow-up period of 63.1 months, ROI was detected at 1.0-120 months after diagnosis in 20 patients, 4 of whom were not receiving glucocorticoid (GC) at the time of ROI. In contrast, DNOI was detected at 5.0-120 months after diagnosis in 15 patients, 8 of whom were not receiving GC at the time of DNOI. In the multivariate analysis, blood eosinophil counts at diagnosis [per 100/µl; hazard ratio (HR) 1.072 (95% CI 1.018, 1.129)] and continuation of GC [vs discontinuation or observation without GC; HR 0.245 (95% CI 0.076, 0.793)] had a significant impact on the time to DNOI, whereas age [HR 0.942 (95% CI 0.899, 0.986)] and ANA positivity [vs negativity; HR 6.632 (95% CI 1.892, 23.255)] had a significant impact on the time to ROI. CONCLUSION: The present study suggests that the risk factors of ROI and DNOI are different in IgG4-RD, highlighting the need for different preventative strategies.

A case of IgG4-related tubulointerstitial nephritis and membranous glomerulonephritis during the clinical course of gastric cancer: Imaging features of IgG4-related kidney disease.

We describe an 81-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with submandibular gland, lymph node, lung, kidney, aortic wall, and prostate lesions with concomitant gastric cancer. After curative surgical treatment of the gastric cancer, corticosteroid therapy for progressively decreasing renal function was started. Before starting steroid therapy, fluorodeoxyglucose positron emission tomography-computed tomography revealed multiple lesions of IgG4-RD but no metastasis of the cancer. However, the patient died 3 months after initiation of corticosteroid therapy because of recurrence of the gastric cancer. In this case, the imaging features of IgG4-tubulointerstitial nephritis dramatically changed during the clinical course of co-existing gastric cancer. The imaging features of the present case may provide clues to the pattern of spread of IgG4 lesions in the kidney.

New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases.

BACKGROUND: The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. METHODS: Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1996 and 2015 in five hospitals by analyzing their baseline clinical features, laboratory, imaging, and pathological test findings, and treatment. RESULTS: Of the 334 patients listed, 205 were male and median age at diagnosis was 65 years. The mean number of organs involved was 3.2 at diagnosis. The most frequently affected organs were the salivary glands, followed by the lacrimal glands, lymph nodes, pancreas, retroperitoneum/periaorta, kidneys, and lungs. The mean serum level of IgG4 was 755 mg/dl, and more than 95% of patients had elevated serum IgG4 levels. The median serum level of C-reactive protein (CRP) was 0.1 mg/dl and the level was less than 1 mg/dl in 90% of patients. A total of 34.7% of patients had low serum levels of C3. Serum levels of C3 and non-IgG4 IgG, calculated as the total IgG minus IgG4, showed an inverse correlation in patients with kidney lesions, while serum IgG4 levels were not correlated with serum C3 levels. Corticosteroid was administered in 78.0% of patients, and was effective in all. CONCLUSIONS: The serum CRP level is generally low and the serum IgG4 level is elevated in most Japanese IgG4-RD patients, in contrast to western patients. These original findings suggest that these two parameters in IgG4-RD differ in some interesting ways from those hitherto reported in western populations. Additional studies, especially international comparative ones, are needed to elucidate the extent and significance of these differences between populations. Attention will also have to be paid to whether the existence of such differences requires consideration when devising international classification criteria.