Tomonori Harada

A Report of Two Cases of Kawasaki Disease Treated With Plasma Exchange

Abstract:  Kawasaki disease is a generalized vasculitis of unknown etiology that occurs predominantly in infants and young children. It is very important to prevent its cardiovascular manifestations, especially coronary artery lesions. Early treatment with intravenous immunoglobulin reduces cardiovascular sequelae, but some patients do not respond to this treatment, and they have a high incidence of coronary artery lesions. On the other hand, acute heart failure is rare in Kawasaki disease. We report on the cases of two patients with persistent fever and shock even after intravenous immunoglobulin therapy. In both cases, plasma exchange may have reduced the risk of coronary artery lesions and proved effective against acute heart failure with catecholamine‐refractory shock; yet the mechanism of this improvement remains unclear.

Henoch-Schonlein purpura presenting duodenal involvement similar to superior mesenteric artery syndrome in a girl

Henoch-Schonlein purpura (HSP) is an inflammatory vasculitis involving the skin, joints, gastrointestinal (GI) tract, and kidneys. This is the first case report describing a 5-year-old girl with HSP presenting duodenal involvement which might be associated with superior mesenteric artery syndrome (SMAS).

Cyclophosphamide followed by mizoribine as maintenance therapy against refractory steroid-dependent nephrotic syndrome

Dear Editor, We read with great interest the articles by Azib et al. [1] and Zagury et al. [2] that recently appeared in Pediatric Nephrology on the long-term prognosis of cyclophosphamide (CPA) for children with steroid-dependent nephrotic syndrome (SDNS). CPA is a classical drug that has been used since the 1970s for treating refractory nephrotic syndrome, such as SDNS, frequent relapsing nephrotic syndrome (FRNS), and steroid-resistant nephrotic syndrome (SRNS) [1, 2] . However, both recent USA guidelines, published in 2009, and the Cochrane Reviews no longer strongly recommend using CPA for SDNS or SRNS because of its relatively low efficacy, gonadal toxicity, and carcinogenicity [3, 4]. Currently, CPA is defined as the third-line drug for SDNS in USA guidelines and is usually used for treating patients with non-steroid dependent FRNS rather than SDNS. The authors of both articles mentioned above as well as authors of a number of previous studies have reported that if CPA is used to treat children with SDNS, a 2-year relapse-free survival of CPA is achieved in 25–42% of patients [1, 2, 5, 6]. To elongate the relapse-free survival by CPA, we prospectively used mizoribine (MZR) as a maintenance therapy after CPA. MZR is a purine metabolism inhibitor that mimics mycophenolate mofetil (MMF). Its efficacy in preventing relapse is not as potent as CPA or cyclosporine (CsA). However, high-dose MZR is broadly used for SDNS and FRNS in Japan because of its safety for long-term use, which is similar to that reported for MMF in the USA [7, 8]. In our study, we treated nine patients with SDNS with 4.4–9.4 mg/kg of MZR, once-daily dosing, beginning on the day following discontinuation of CPA, and observed the patients for 2 years. Of these nine patients, six had already tried CsA prior to CPA, but they had discontinued CsA because of primary resistance to CsA (n=3), secondary resistance to CsA, or so-called tachyphylaxis (n=2), and posterior reversible encephalopathy syndrome (PRES, n=1), suggesting that most of the patients suffered refractory SDNS. We observed that six of the nine children (66%) achieved 2-year relapse-free survival (Table 1). This rate is much better than that reported for single therapy with CPA [1, 2, 5, 6]. Among the six patients who did not relapse during the 2year follow-up, four patients no longer experienced relapse even after subsequent discontinuation of MZR. One patient still infrequently relapsed while MZR treatment, and one patient returned to SDNS and was successfully treated with rituximab later. No serious adverse events were observed with MZR treatment. We chose MZR as a maintenance therapy after CPA. However, MMF has a similar pharmacological structure and mechanism to MZR and may also be a better candidate for S. Ito (*) :K. Kamei Division of Pediatric Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157–8535, Japan e-mail: ito-shu@ncchd.go.jp

Mizoribine for renal sarcoidosis: effective steroid tapering and prevention of recurrence

Sarcoidosis is a systemic disease of unknown etiology that is characterized by chronic non-caseating granulomatous inflammation with tissue destruction. It is an uncommon disease in children, and renal sarcoidosis in particular is very rare in adults and children. A 17-year-old boy with renal sarcoidosis was referred to our hospital with an initial diagnosis of pyelonephritis. Prior treatment with various antibiotics had not been effective, but tentative oral daily prednisolone (PSL) had partially ameliorated his symptoms, although the symptoms recurred during steroid tapering. We detected non-caseating granulomatous interstitial nephritis and numerous sclerotic glomeruli in a second biopsy specimen, compatible with the diagnosis of renal sarcoidosis. The patient was treated with pulsed methyl-prednisolone and oral daily doses of PSL and mizoribine (MZR). During the treatment with MZR, the PSL was successfully tapered, and the patient has since presented no signs of recurrence. Our treatment of this patient shows that treatment with MZR can allow steroid sparing and prevent recurrence in a patient with sarcoidosis.

Superior mesenteric artery syndrome: risk factor for duodenal involvement in Henoch-Schönlein purpura.

Background:  The anatomical location of the third portion of the duodenum is between the superior mesenteric artery (SMA) and the abdominal aorta (AA). When the aorto‐mesenteric angle (AMA) is small and the aorto‐mesenteric distance (AMD) is short, the duodenum becomes tightly compressed between these two blood vessels. Severe compression can obstruct the duodenum, resulting in vomiting and abdominal pain. This clinical condition is termed superior mesenteric artery syndrome (SMA syndrome). The duodenum is frequently affected in Henoch–Schönlein purpura (HSP). The aim of the present study was to verify that duodenal anatomy mimicking SMA syndrome is a risk factor for duodenal involvement and abdominal pain in HSP.

GI involvement of sigmoid mucosal erosion in a 13-year-old girl with microscopic polyangiitis

endobiliary RFA can completely obviate the need for an SEMS. Until now, photodynamic therapy was the only evidencebased endoscopic treatment other than stenting that improved the quality of life and survival of such patients.5 Endobiliary RFA adds to the endoscopic armamentarium for the treatment of these subjects. However, further randomized controlled trials are needed to establish improved SEMS patency, cost-effectiveness, and survival advantages, if any. In conclusion, endobiliary RFA seems to be a userfriendly and effective palliative treatment modality for paFigure 4. Cholangiogram obtained 2 weeks after the use of endoscopic RFA.

Extended-spectrum beta-lactamase-producing bacteria and vesicoureteral reflux in children

We encountered two children with vesicoureteral reflux (VUR) and urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria. Beta-lactamases open the beta-lactam ring of antibiotics and confer resistance to antibiotics. In the 1960s and 70s beta-lactamases conferred resistance to penicillins and narrow spectrum cephalosporins, such as cephalothin or cefazolin. The secondand third-generation cephalosporins, with an oxyimino side chain such as cefotaxime (CTX), ceftazidime (CAZ), ceftriaxone (CTRX) and cefepime (CFPM), were effective against beta-lactamase-producing bacteria in those years. Soon after CTX started to be used in Europe, Klebsiella pneumoniae (K. pneumoniae) with transferable resistance to oxyimino-cephalosporins (CTX, CAZ, and CTRX) by plasmid were isolated in Germany. Mutational evolution of plasmid-mediated beta-lactamases conferred resistance to these higher generation cephalosporins and monobactam aztreonam (AZT), and they were named extended-spectrum beta-lactamases (ESBL). Infections with ESBL-producing bacteria are associated with a poor prognosis in adults. Additionally, the prevalence of ESBL-producing bacteria has been increasing year by year not only in America and Europe but even in Japan. There have been many reports of UTI by ESBL-producing bacteria in adults. However, ESBL-producing bacteria recently started to become pathogens of UTI in children. We had difficulty in treating UTI by ESBL-producing bacteria in two babies with VUR. It seems infections by ESBL-producing bacteria will seriously affect the management of UTI in children in future.

Anatomical condition mimicking superior mesenteric artery syndrome might cause duodenal involvement in Henoch–Schönlein purpura

The authors thank Dr Fujii for his voluminous contribution to the literature in general and to our article in particular. The excellent and comprehensive discussion in his letter of the anatomical condition similar to superior mesenteric artery syndrome (SMA) and duodenal lesion in Henoch–Schönlein purpura (HSP) provides an illuminating framework on our study. We would like to offer a few comments. Dr Fujii indicated that HSP patients with abdominal pain and duodenal lesion by ultrasound showed hypoperistalsis, which was not consistent with characteristics of SMA syndrome. We have also observed bowel abnormalities (BA) on ultrasound in HSP that were inflammatory, and paralytic findings of the intestine. Thus, in our manuscript, BA were defined as bowel wall thickness of more than 3 mm and signs of paralytic ileus, such as hypoperistalsis of thickened bowel and bowel fluid stagnation in the proximal side, which differ from small bowel series criteria for SMA syndrome. We referred to ultrasound criteria for SMA syndrome, only to emphasize and explain the correlation between the anatomical condition mimicking SMA syndrome and duodenal involvement in HSP, not to diagnose SMA syndrome. Moreover, we are afraid that duodenal BA never develop merely due to the anatomical condition mimicking SMA syndrome, and we think BA develop due to this anatomical condition concomitant with systemic leukocytoclastic vasculitis. As described in our manuscript, ultrasound criteria for SMA are just one set of the required criteria to diagnose SMA syndrome. In one of twelve HSP patients with abdominal pain and duodenal lesions by ultrasound in our study, we measured the aortomesenteric angle (AMA) and the aortomesenteric distance (AMD) both on admission and at the time of discharge. Decrease of AMA (23°→12°) and AMD (5.3 mm→3.3 mm) at the time of discharge compared with those on admission was observed in this patient, because bowel edema resolved after prednisolone therapy. We used the values of AMA and AMD measured on admission in all HSP patients in our study. The difference between patients and controls might have been more significant in AMA and AMD after resolution of intestinal edema, if we had adopted the values at the time of discharge or the asymptomatic state in all HSP patients. Thus, the significant differences in AMA and AMD between the two groups would not be overestimated but rather underestimated. Strictly speaking, we should adopt the values at the asymptomatic state, not the edematous state, because we would research the causality of duodenal lesion in an HSP patient with abdominal pain. However, since the number of HSP patients assessed in our study was small, we are now planning an extended study.

Efficacy of mycophenolate mofetil for steroid and cyclosporine resistant membranoproliferative glomerulonephritis type I

Sirs, We read with great interest the article entitled “Remission of resistant MPGN type I with mycophenolate mofetil and steroids” by De et al. [1]. We encountered a similar case and would like to comment on the efficacy of mycophenolate mofetil (MMF) for refractory membranoproliferative glomerulonephritis (MPGN) type I. A 13-year-old boy was transferred to our hospital because of steroid-resistant nephrotic syndrome with hypocomplementemia. He had been treated with 2 mg/kg of prednisolone (PSL) for 4 weeks, but systemic edema, massive proteinuria and hypertension had not improved. When he was admitted to our hospital, the results of urinalysis were: protein 2,498 mg/dl, creatinine 399 mg/dl, β2 microglobulin 5,691 μg/dl (normal <250 μg/dl), and red blood cell (RBC) count over 50 per high-power field (HPF). Those of blood biochemistry were: 4.4 g/dl of total protein, albumin 2.0 g/dl, serum creatinine 0.83 mg/dl, blood urea nitrogen 33 mg/dl, uric acid 7.3 mg/dl, total cholesterol 404 mg/dl, triglycerides 296 mg/dl, complement (C)3 21 mg/dl (86~160 mg/dl), C4 21 mg/dl (17~45 mg/dl), CH50 20 U/ml (30~40 U/ml), anti-nuclear antibody (negative), and anti-double stranded DNA antibody (negative). Renal biopsy showed diffuse and severe MPGN type I. All the glomeruli showed marked lobulation, intracapillary hypercellularity, thickening of the capillary walls and double contour. Immunofluorescence showed intense staining of all capillary walls and mesangial cells with C3 and immunoglobulin (Ig)G. An electron micrograph showed electron-dense deposits only in the subendothelial space. The patient was initially treated with three courses of methyl prednisolone pulse therapy (MPT, one course; 1 g of methyl prednisolone for 3 days) followed by PSL orally. Lisinopril and losartan were used for hypertension and proteinuria. Proteinuria was dramatically reduced after three courses of MPT, but it was still in the nephrotic range (Fig. 1). Additional cyclosporin was also insufficient to induce remission of proteinuria. In the end, he was started on MMF 3 months from the initiation of treatment. Proteinuria decreased promptly soon after he had started on MMF. Two months later the proteinuria had completely resolved, even though PSL had been withdrawn. Under treatment with PSL, cyclosporin A (CsA) and MMF, he has not had proteinuria for 8 months. Hematuria has also Pediatr Nephrol (2009) 24:1593–1594 DOI 10.1007/s00467-009-1141-x