Kisei Minami

A neonatal case of chronic granulomatous disease, initially presented with invasive pulmonary aspergillosis

Chronic granulomatous disease (CGD) often presents with infectious illness, such as repeating bacterial and fungal infections, due to the inability to generate superoxide, which would destroy certain infectious pathogens, and is usually diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who initially presented with invasive aspergillosis. Neonatal invasive pulmonary aspergillosis is very rare and, to the best of our knowledge, this might be the youngest case in Japan.

Case report of a 6-year-old girl with Mycoplasma hominis ventriculoperitoneal shunt infection

Mycoplasma hominis is a rare causative pathogen for surgical site infections after neurosurgical procedures. This organism lacks a cell wall, rendering it undetectable by Gram staining and making it resistant to beta-lactam antibiotics. In addition, some special techniques are required to identify this organism. Thus, it is very difficult to diagnose infections caused by this pathogen. Here, the authors report a pediatric case of M. hominis ventriculoperitoneal shunt (VPS) infection with central nervous system involvement for which beta-lactam antibiotics were not effective and Gram staining revealed no pathogens. Because few cases have been described that involve the treatment of M. hominis infection after neurosurgery, in this case the patients serum and CSF were monitored for antibiotic drug concentrations. Successful treatment of the infection was achieved after approximately 6 weeks of administration of clindamycin and ciprofloxacin antibiotics in addition to external ventricular drain revision and subsequent VPS replacement. When beta-lactam antibiotics are ineffective and when Gram staining cannot detect the responsible pathogens, it is important to consider M. hominis as the atypical pathogen.

Four Sporadic Pediatric Cases of Yersinia enterocolitica O:8 Infection in a Rural Area of Japan

In the spring of 2015, we experienced a cluster of 4 sporadic cases of yersiniosis in children in Nagano prefecture, a rural area of Japan. Two patients developed appendicitis-like episodes; one had acute gastroenteritis, and the other had bacteremia associated with liver abscess. The causative agent of these infections was Yersinia enterocolitica serogroup O:8. None of the patients had an underlying illness, and all have recovered completely. The patients were neither socially nor geographically related to each other. These 4 consecutive cases suggest that Y. enterocolitica O:8 has spread substantially in the middle part of Japan, and that this virulent strain might be more common than previously reported in our country.

Early diagnosis of early-onset sarcoidosis: a case report with functional analysis and review of the literature

This study examined the pathogenesis of early-onset sarcoidosis (EOS) in a patient with a rare NOD2 mutation and surveyed the literature to identify the hallmark features for early diagnosis. An infant girl suffering from prolonged fever and skin rash of multiple pinkish papules and subsequent erythema nodosum was referred to our institution. Skin biopsy and DNA sequencing were performed along with cytokine profiling of the patient’s serum and stimulated mononuclear cells. NF-κB activation was analyzed using transfected cells. Multiple non-caseating granuloma inclusions were recognized in biopsy specimens obtained from the patient’s rash. DNA sequencing revealed a very rare heterozygous Met513Thr (M513T) mutation in NOD2. Mononuclear cells produced a low amount of IL-1β upon stimulation as compared with normal control cells. Mutated NOD2 transfection enhanced NF-κB activation. We suspected that the M513T mutation in NOD2 decreased IL-1β production and enhanced NF-κB activation, which was likely responsible for the patient’s granuloma involvement. A comprehensive review of the literature on 30 cases of sporadic type of EOS revealed that all patients had cutaneous manifestations, with all but one displaying granulation. A majority of EOS patients have R334W/Q. But about half of sporadic EOS had NOD2 mutations other than R334W/Q, as in the present case. Accordingly, skin rash with granuloma formation and specific NOD2 mutations may represent early diagnostic hallmarks of EOS in infants with persistent inflammation.

Transient Deformation of Neutrophils in Kawasaki Disease.

In the treatment of Kawasaki disease, resistance to high-dose immunoglobulin intravenous (IGIV) can occur. The neutrophil morphology analyses in 17 patients revealed that transient pseudo-Pelger-Huët anomaly was more frequently detected in the IGIV-resistant group. This finding may aid the prediction of IGIV resistance.

A PEDIATRIC CASE OF BACTEREMIA AND POSSIBLE CHOLECYSTITIS, DUE TO MORAXELLA OSLOENSIS

We encountered a pediatric case of bacteremia and possible cholecystitis due to Moraxella osloensis that was treated successfully. We confirmed the diagnosis with the presence of a high serum titer of the antibody to the organism. Furthermore, 16S rRNA sequencing was performed to identify the bacteria.

Asymptomatic subcutaneous cervical mass due to Actinomyces odontolyticus infection in a pyriform sinus fistula

A 2-year-old boy presented with a left-sided, anterior cervical subcutaneous mass. The patient had no remarkable family or past history and no other accompanying symptoms. T2-weighted magnetic resonance imaging of the mass at a previous hospital showed an apparently circumscribed mass (Fig. 1a). The patient was referred to Nagano Children’s Hospital with suspected malignant disease. On admission, the mass was hard and minimally mobile. The patient reported no burning sensation or tenderness. Oral hygiene was good. Laboratory results were as follows: white blood cell count, 11.0 9 10/L; C-reactive protein, 0.05 mg/dL; and erythrocyte sedimentation rate, 20 mm/h. Five days after admission, biopsy of the cervical subcutaneous mass was performed under general anesthesia, after which a course of sulbactam/ampicillin was initiated because an infection was suspected on the basis of intraoperative rapid diagnosis. On the final pathology, although a large number of neutrophils were observed, monoclonal cell proliferation was not detected. Moreover, because sulfur granules (druse) were observed in a single field of one specimen (Fig. 1c), Actinomyces infection was suspected. Therefore, the biopsy specimen was analyzed for 16S rRNA gene amplification and sequencing using Actinomyces-specific primers. The final diagnosis was Actinomyces odontolyticus infection. Although the routine bacterial culture did not show Actinomyces infection, co-growth of a-Streptococcus and Eikenella corrodens was observed. Although the detected bacteria are oral inhabitants, there was no evidence of gingival disease, oral trauma, dental caries, or extraction. Symptoms improved with antibiotic treatment, and the patient was discharged 14 days after admission. He continued oral antibiotics therapy with amoxicillin/clavulanate for 6 months, and the symptoms completely resolved. At a later date, barium esophagography showed a pyriform sinus fistula (PSF) in the area of the subcutaneous abscess (Fig. 1b). Actinomyces is a Gram-positive facultative anaerobe and an endogenous flora of the oral cavity. Actinomyces infection, particularly cervicofacial actinomycosis, is rare in children. On the basis of a previous review of 17 pediatric cervicofacial actinomycosis cases, clinical features include disease development at any age in children, a higher frequency in girls, and an association with pain and fever. Clinical diagnosis is reached on histopathological confirmation of typical sulfur granules, positive culture, and/or isolation of Actinomyces species. Although the most predominant organism was A. israelii, only one patient reported A. odontolyticus infection as the cause. Actinomycosis, however, remains a diagnostic challenge. Microbiological identification is often difficult because this organism grows slowly and, thus, careful anaerobic culturing is required. On microscopy the lesions have an outer zone of granulation, consisting of collagen fibers and fibroblasts, and a central purulent focus containing neutrophils that surround the sulfur granules. Diagnosis on radiology is difficult because the findings of actinomycosis are non-specific. Therefore, in clinical practice, lack of responsiveness to empirical antibiotic therapy, presentation of a chronic palpable mass, difficulty in establishing a microbiological diagnosis, and imaging showing a soft-tissue mass make differentiating this mass from a neoplasm, granulomatous disease, or other infectious disease at initial presentation difficult. Although sulfur granules were observed in the present case, which led to suspicion of Actinomyces infection, a diagnosis of A. odontolyticus is considered to be more difficult because granules are usually absent in A. odontolyticus. Therefore, 16S rRNA-specific polymerase chain reaction using specimen or colony extraction may be important for making a correct diagnosis in a shorter period. The clinical utilization of this approach may require further validation. Pyriform sinus fistula represents an anomaly of the opening of the third and fourth branchial pouches in the pyriform sinus. PSF is often found in association with suppurative thyroiditis, recurrent neck abscess, odynophagia, and, occasionally, dyspnea. One report indicated that Streptococcus mitis was most commonly associated with PSF in pediatric patients, whereas Klebsiella pneumoniae was most commonly Correspondence: Ryu Yanagisawa, MD PhD, Division of Blood Transfusion, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Email: ryu@shinshu-u.ac.jp Received 2 November 2016; revised 21 April 2017; accepted 1 May 2017. doi: 10.1111/ped.13321

Infective endocarditis due to multiple species of anaerobes following tricuspid valve replacement

A 24-year-old woman presented to the Nagano Children’s Hospital complaining of recurrent fever and malaise. Ebstein’s anomaly had been diagnosed at birth. Three months prior to admission, her tricuspid regurgitation had deteriorated and the defective valve was replaced with a biological valve. She was discharged 3 weeks after the operation uneventfully. Three weeks later, she developed a low-grade fever and oral antibiotics were prescribed. However, the patient’s fever failed to respond stably. On admission to our hospital (Day 0), her body temperature was 40.1 C, blood pressure was 118/79 mmHg, pulse rate was 102 bpm, and her respiratory rate was 28 breaths/min. General appearance indicated malaise, and a systolic ejection murmur (III/VI) was heard. Transthoracic echocardiography was performed subsequently, revealing a 25 mm 15 mm vegetation on the replaced tricuspid valve. Vancomycin and gentamicin were started immediately and tricuspid valve re-replacement was performed on Day1. The Gram stain of the vegetation showed a polymicrobial pattern with multiple morphotypes strongly suspected of being anaerobes. We switched the antibiotic regimen from vancomycin/gentamicin to vancomycin/

Effectiveness of subarachnoid drug infusion for pediatric tumor-related pain

Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14‐year‐old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girls pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post‐mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side‐effects, even in the field of pediatric palliative care.