High serum IgA levels in patients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, and favourable responses to treatments.

OBJECTIVES: Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels. METHODS: The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels. RESULTS: Of the 169 patients with IgG4-RD, 17 (10.1%) had elevated serum IgA levels. Those with elevated serum IgA levels showed higher serum C-reactive protein levels and lower prevalence of relapse than those without. Other clinical features did not differ significantly, including inclusion scores of the American College of Rheumatology/European League Against Rheumatism classification criteria. Cox regression analysis showed that elevated serum IgA levels were associated with a lower incidence of relapse. Moreover, patients with elevated serum IgA levels showed prompt improvement in response to glucocorticoids in the IgG4-RD responder index. CONCLUSIONS: Some patients diagnosed with IgG4-RD have high serum IgA levels. These patients may form a subgroup, characterized by good response to glucocorticoids, less frequent relapse, mildly elevated serum C-reactive protein levels, and possible complications of autoimmune diseases.

De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report.

BACKGROUND: Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. CASE PRESENTATION: We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. CONCLUSIONS: SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.

Development of IgG4-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy: A case report.

This report describes a patient diagnosed with immunoglobulin G4 (IgG4)-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy. A 48-year-old Japanese woman presented with fatigue and leg oedema. Computed tomography showed perigastric lymphadenopathy, for which she underwent a laparoscopic biopsy of the perigastric lymph nodes. Although histopathological examination of the lymph nodes did not lead to a definitive diagnosis, serological tests revealed elevated serum IgG4 levels (558 mg/dl) and IgG4 immunostaining of the lymph nodes showed IgG4-positive plasma cell infiltration, leading to the suspicion of IgG4-related disease. Further workup revealed no organ lesion other than lymphadenopathy. At age 55 years, despite having no subjective symptoms, contrast-enhanced computed tomography showed low-density lesions in the tail of the pancreas and the left kidney. Histopathological examination showed lymphocyte infiltration, consisting of a mixture of plasma cells and eosinophils, in both organs and obliterative phlebitis in the pancreas. IgG4 immunostaining of the kidney specimens showed 160 IgG4-positive cells per high-powered field, with the IgG4+/IgG+ cell ratio being almost 100%, leading to a diagnosis of IgG4-related pancreatitis and kidney disease. Treatment with prednisolone for 2 months resulted in lesion improvement. Although the diagnosis of IgG4-related lymphadenopathy is often challenging in patients with lymphadenopathy alone, findings in the present patient emphasise the importance of long-term follow-up, as it may allow early detection of involvement of other organs by IgG4-related disease.

Clues to mortality trends and their related factors in IgG4-related disease: A Japanese single-centre retrospective study.

OBJECTIVES: This study aimed to clarify mortality trends and their related factors in immunoglobulin G4-related disease (IgG4-RD) with various organ involvement. METHODS: We retrospectively reviewed the medical records of patients with IgG4-RD at a single rheumatology centre in Japan. We calculated the standardized mortality ratio using Japanese national mortality statistics. Cox regression analyses were also performed to assess mortality-related factors. RESULTS: A total of 179 patients with IgG4-RD were included with a median follow-up period of 47 months. The standardized mortality ratio in our cohort was 0.86 (95% confidence interval 0.41-1.59). Univariate Cox regression analyses indicated that the number of affected organs at diagnosis (hazard ratio 1.45, 95% confidence interval 1.02-2.05), estimated glomerular infiltration rate <45 ml/min/1.73 m2 at diagnosis (vs. ≥45, hazard ratio 8.48, 95% confidence interval 2.42-29.79), and the presence of malignancy during the clinical course (hazard ratio 5.85, 95% confidence interval 1.62-21.15) had a significant impact on the time to death. CONCLUSIONS: Our findings suggest that in the rheumatology department, IgG4-RD does not significantly affect long-term patient survival. However, multi-organ involvement, renal dysfunction, and malignancy may be associated with higher mortality trends in IgG4-RD. Early detection and appropriate management of risk factors may improve the long-term prognosis of patients with IgG4-RD.

[Lipomatous Hypertrophy of the Interatrial Septum Preoperatively Misdiagnosed as Right Atrial Lipoma].

A 73-year-old man with a right atrial tumor and a distal aortic arch aneurysm was scheduled for tumor resection and total arch replacement (TAR). Although the tumor was diagnosed as an intraatrial lipoma preoperatively, it could not be differentiated from an infiltrating lipoma on the basis of intraoperative pathological examination. We decided to completely excise the tumor. However, we found intraoperatively that the tumor was contiguous with the epicardial fat tissue of the heart, strongly suggesting a lipomatous hypertrophy of the interatrial septum (LHIS). Thus, we discontinued the resection, reconstructed the atrial septum and right atrial wall, and performed TAR with a frozen elephant trunk technique. Although the patient required temporary continuous hemodiafiltration because of his preoperative renal dysfunction, he was discharged 30 days postoperatively. If LHIS was the preoperative diagnosis, only an incisional biopsy was needed for diagnosing this case. However, LHIS is quite rare in Japan. Therefore, awareness of the disease and meticulous analysis of preoperative heart imaging are important to avoid an unnecessary surgery.

Risk of Out-of-Hospital Cardiac Arrest in Aged Individuals in Relation to Cold Ambient Temperature　- A Report From North Tochigi Experience.

BACKGROUND: The impact of cold ambient temperature on out-of-hospital cardiac arrest (OHCA) in aged individuals caused by cardiovascular events in indoor environments has not been investigated sufficiently.Methods and Results:We conducted a case-crossover study. The relationship between OHCA caused by cardiovascular events and exposure to minimum temperature <0℃ was analyzed. Conditional logistic regression analysis was performed to estimate the odds ratios for the relationship between exposure to minimum temperature <0℃ and the risk of OHCA. Between January 1, 2011, and December 31, 2015, a total of 1,452 cases of OHCA were documented, and patients were screened for enrollment. A total of 458 individuals were enrolled in this analysis, and were divided into 2 groups of 110 (elderly group: 65-74 years old) and 348 (aged group: ≥75 years old). The aged individuals had a significant increased risk of OHCA after exposure to minimum temperature <0℃ (odds ratio [OR]: 1.528, 95% confidence interval [CI] 1.009-2.315, P=0.045). Cold ambient temperature was an especially significant increased risk for OHCA occurrence for males (OR: 1.997, 95% CI 1.036-3.773, P=0.039) and during winter (OR: 2.391, 95% CI 1.312-4.360, P=0.004) in the aged group. CONCLUSIONS: Cold ambient temperature significantly affected aged individuals (≥75 years old) experiencing an OHCA caused by cardiovascular events in indoor environments.