Sayaka Ishikawa

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis.

To assess the role of interleukin (IL)-33 and ST2, the receptor for IL-33, in the pathogenesis of systemic juvenile idiopathic arthritis (s-JIA), we sequentially measured the serum levels of IL-33 and soluble ST2 (sST2) in patients with s-JIA and determined their correlation with measures of disease activity and severity. Twenty-four patients with s-JIA, 5 with rheumatoid factor positive polyarticular JIA (RF+poly-JIA), and 20 age-matched healthy controls (HCs) were analyzed. IL-33 and sST2 levels were quantified in serum by enzyme-linked immunosorbent assays. Serum IL-33 levels in most patients with active s-JIA were below the lowest detection limit. Serum IL-33 levels in patients with RF+poly-JIA were significantly higher than those in patients with s-JIA and HC. Serum sST2 levels in patients during the active phase of s-JIA were much higher than those in patients with poly-JIA and HC. Serum sST2 levels in patients with s-JIA were significantly elevated even in the inactive phase, when other clinical parameters were normalized. Serum sST2 levels correlated positively with the clinical parameters of disease activity. These findings indicate that ST2 may be an important mediator in s-JIA. Serum sST2 levels in patients with s-JIA correlated with disease activity, suggesting a potential role as a promising indicator of disease activity.

Distinct cytokine profile in juvenile systemic lupus erythematosus-associated macrophage activation syndrome

Macrophage activation syndrome (MAS) has been observed in patients with systemic lupus erythematosus (SLE). Recognition of MAS in patients with SLE may be particularly challenging because it may mimic the clinical features of the underlying disease or be confused with an infectious complication. Massive hypercytokinemia is strongly associated with the pathogenesis of systemic lupus erythematosus-associated macrophage activation syndrome (SLE-MAS) but the pathogenesis and kinetics of cytokine release in SLE-MAS patients is not well studied. We present a case of SLE-MAS. The patient showed the distinct cytokine profile of SLE-MAS compared to systemic juvenile idiopathic arthritis associated MAS and Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis. The observed TNF-α dominant increase appears to be characteristic of SLE-MAS. IgM type antilymphocyte antibody (ALAB) was detected on the surface of lymphocytes during the acute phase and disappeared when the patient was in remission. The patient had a heterozygous P369S-R408Q mutation in the MEFV gene. Our results suggest that ALAB and a MEFV mutation might play important roles in the pathogenesis of SLE-MAS. Furthermore, the cytokine profile of SLE-MAS differs from that of S-JIA-MAS: the TNF-α dominant increase appears to be characteristic.

Tolvaptan therapy for massive edema in a patient with nephrotic syndrome

BackgroundNephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema. The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.Case-Diagnosis/TreatmentWe present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.ConclusionsTolvaptan is effective for the treatment of massive edema caused by NS. Larger studies are needed in the future to fully assess the value and safety of tolvaptan use for this condition.

Successful treatment with tocilizumab of a psoriasiform skin lesion induced by etanercept in a patient with juvenile idiopathic arthritis.

To the Editor, A 20-year-old woman presented with arthritis of the left elbow at 14 years of age. The arthritis extended to the left wrist and left knee, leading to reduced mobility and difficulty ...

Accumulation of mature B cells in the inflamed muscle tissue of a patient with anti-155/140 antibody-positive juvenile dermatomyositis

We report the first case of a Japanese patient with anti-155/140 antibody-positive juvenile dermatomyositis (JDM). Her clinical features included severe cutaneous involvement. Serum B cell-activating factor levels were significantly increased. Mature class-switched memory B cells accumulated in inflamed muscle tissue but decreased in peripheral blood. These findings indicate that loss of B cell tolerance and accumulation of mature B cells in inflamed muscle tissue play an important role in the pathogenesis of JDM.

Rotavirus gastroenteritis‐associated urinary ammonium acid urate crystals

Although ammonium acid urate (AAU) calculi are extremely rare renal stone components, it was recently found that many urinary tract calculi that cause post‐renal renal failure in rotavirus (RV) gastroenteritis are AAU calculi. The mechanism of AAU calculi development in RV gastroenteritis has not been fully elucidated. We analyzed data from eight RV gastroenteritis patients who transiently had AAU crystals in their urinary sediment. In these patients, formation of AAU crystals occurred earlier than the formation of AAU calculi. No difference was observed in serum and urine uric acid levels between RV gastroenteritis patients with or without AAU crystals. Interestingly, fractional excretion of sodium was extremely low among patients with AAU crystals. These results suggest that the formation of AAU crystals might not be due to excretion of uric acid, but excretion of sodium.

Urinary neopterin: an immune activation marker in mesangial proliferative glomerulonephritis

BackgroundTo clarify in vivo neopterin expression within the human kidney and its clinical role as a biomarker for immune complex-mediated mesangial proliferative glomerulonephritis (mesPGN) in children.MethodsWe examined neopterin expression within the kidneys of 14 patients with mesPGN and five patients with minimal changes. We also measured the serum and urinary neopterin levels in fourteen patients with mesPGN and sixteen age-matched healthy controls and correlated the histological findings and clinical features.ResultsNeopterin expression was observed within the distal tubular epithelial cells. It was induced within the glomerular endothelial cells and infiltrated CD68-positive macrophages in the glomeruli and interstitial areas. Furthermore, urinary neopterin levels were significantly elevated and positively correlated with histopathological findings and the degree of proteinuria.ConclusionsThese findings indicate that increased urinary neopterin may reflect macrophage activation and active inflammation within the kidney in immune complex-mediated glomerulonephritis. Neopterin may thus represent a useful biomarker of immune complex-mediated glomerulonephritis in the clinical setting.

An infant with PELVIS (perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag) syndrome misdiagnosed as diaper rash.

Figure. External genitalia of the patient. A 1-month-old boy was evaluated for a “refractory diaper rash.” He had been born at full term after an uneventful gestation. During the newborn period, he was noted to have multiple erosions and ulcers in the perineal area that were diagnosed as severe diaper rash. Examination of external genitalia revealed a bifid scrotum. His anus was displaced anteriorly and toward the left, and a right-sided cutaneous recess resembling an anus was identified. Purplish discoloration (erythema and telangiectasia) in the perineal area was observed. This lesion gradually increased in size and became a perineal hemangioma (Figure). The patient’s constellation of findings led to a diagnosis of mild variant of PELVIS (perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag) syndrome. Magnetic resonance imaging confirmed the presence of a perineal hemangioma and showed no gross anomalies in other visceral structures, including spine and urinary tract. Imperforate anus was surgically corrected at 2 months of age. Hemangiomas are the most common benign tumors of infancy, occurring in up to 10% of children by 1 year of age. Although hemangiomas may occur on any part of the body, they demonstrate a striking predilection for the head and neck region. Approximately 10% of hemangiomas are located in the perineal area. Perineal hemangiomas are more prone to ulceration because of irritation from stool, urine, friction, and maceration. In rare instances, perineal hemangiomas can be associated with congenital anomalies, including anorectal, urinary tract, spine, and external genitalia malformations. This association was proposed as PELVIS syndrome to tie together the syndrome with the following abnormalities: perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag. Perineal hemangiomas should alert the physician to possible underlying abnormalities and trigger a comprehensive examination for PELVIS. n

Multiple osteonecrosis in a patient with juvenile systemic lupus erythematosus.

A 15-year-old girl with systemic lupus erythematosus (SLE) presented with mild pain of her left lower extremity. She had received high-dose corticosteroids for about 7 months after the onset of her disease. Plain radiography of femurs, tibias, and fibulas showed no significant findings. Magnetic resonance imaging of the left lower extremity demonstrated multiple areas of osteonecrosis with hyperintensity on T1-weighted image (Figure, A) and hypointensity on the T2-weighted fat-suppressed image (Figure, B) at the left femur and tibia. Awhole-body bone scan showed multiple hot areas at bilateral humeri, femurs, and tibias. The patient used a weight-bearing orthosis, and her pain of the left lower extremity was relieved. The prevalence of osteonecrosis in patients with SLE has been reported to range from about 5% to 40%. Multiplicity was observed in about 70% of patients on bone scintigraphs. The onset of symptoms in osteonecrosis is usually gradual with mild or vague pain in patients with SLE. Plain radiography is insufficient for early diagnosis and for the evaluation of osteonecrosis. Magnetic resonance evaluation may be appropriate in high-risk patients.

A distinct lymphocyte distribution in relapse after rituximab for steroid-dependent nephrotic syndrome

Rituximab (RTX) is a new steroid-sparing therapy for childhood steroid-dependent nephrotic syndrome (NS). However, relapses frequently occur immediately after CD19 recovery. We report the cases of two steroid-dependent NS patients treated with RTX followed by mizoribine (MZB). One patient relapsed, and the other developed proteinuria after CD19 recovery until the MZB was replaced by mycophenolate mofetil. These patients exhibited different lymphocyte phenotypes, with the CD4+/CD8+ profile favoring CD8+ T lymphocytes, while CD3+ HLA-DR-expressing activated T lymphocyte expansion occurred in the relapsed patient. Based on these findings, we suggest that T cell activation may influence outcome and that phenotypic analysis in addition to B cell monitoring may facilitate the detection of NS relapse.