Correction: Conjunctivitis, the key clinical characteristic of adult rubella in Japan during two large outbreaks, 2012-2013 and 2018-2019.

[This corrects the article DOI: 10.1371/journal.pone.0231966.].

Comparison of 18F-FDG PET/CT and 67Ga-SPECT for the diagnosis of fever of unknown origin: a multicenter prospective study in Japan.

OBJECTIVE: The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). METHODS: The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient's attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. RESULTS: A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5-37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P < 0.001). CONCLUSIONS: FDG-PET/CT showed a superior sensitivity to 67Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.

Conjunctivitis, the key clinical characteristic of adult rubella in Japan during two large outbreaks, 2012-2013 and 2018-2019.

BACKGROUND: Rubella virus infection mainly causes illness with mild fever, rash, and lymphadenopathy in children; however, the clinical characteristics of adult rubella are not well-known. METHODS: An observational study was conducted to compare the characteristics between adult rubella and adult non-rubella among participants aged ≥18 years, with suspected symptomatic rubella. Participants were screened for rubella-specific IgM expression using an enzyme immune assay kit, at a tertiary care hospital in Japan during two outbreaks (January 2012-December 2013 and January 2018-March 2019). Adult rubella diagnosis followed strong positive or paired rubella-specific IgM expression or positive rubella-specific reverse-transcription-polymerase chain reaction. Patients aged <18 years or with clinically suspected rubella with weak or negative IgM expression were excluded. RESULTS: Overall, 82 adult rubella and 139 adult non-rubella, with a median age (interquartile range) of 31 (25-41) years and 34 (27-42) years, respectively, were included. Multivariate analysis showed that conjunctivitis (odds ratio 80.6; 95% confidence interval 13.4-486.3; P <0.001) and male sex (odds ratio 7.1; 95% confidence interval 1.8-28.1; P = 0.005) were significantly associated with adult rubella. Among men born from 1962 to 1979 (high-risk population, n = 68), conjunctivitis also showed a significant association with adult rubella in the multivariate analysis (odds ratio 24.2; 95% confidence interval 1.1-553.7; P = 0.046) as these patients were not included in the national vaccination program. There was no difference in the clinical characteristics between one-time vaccination (n = 11) and no vaccination (n = 8) patient in the adult rubella group. CONCLUSIONS: Conjunctivitis was the key clinical symptom associated with adult rubella. For the early diagnosis of adult rubella, clinicians should focus on assessing conjunctivitis in patients.

GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection.

We report a case of a 27-year old woman with persistent fever and pancytopenia who had multiple episodes of a hemophagocytic lymphohistiocytosis (HLH) like condition. The criterion for HLH was satisfied; primary cytomegalovirus (CMV) infection was identified as the cause. Further examination revealed a GATA binding protein 2 mutation. Reports of GATAs deficiency presenting with HLH after primary CMV infection is very limited. As early recognition and diagnosis will improve patients' outcomes, internists and infectious disease specialists should be aware of this disease.

Real-time PCR investigation of the prevalence of Fusobacterium necrophorum in patients with pharyngitis in Japan.

PURPOSE: Recent data suggest an association between Fusobacterium necrophorum infection and pharyngotonsillitis among adolescents and adults. However, existing reports are only from North America and Europe. We aimed to identify and compare the prevalence of F. necrophorum among patients with pharyngitis and asymptomatic controls in Japan and clarify the epidemiological characteristics of pharyngitis. METHODS: Patients aged ≥16 years with pharyngitis and asymptomatic controls were prospectively included. F. necrophorum was detected by using both conventional culture methods and real-time F. necrophorum-specific PCR targeting the rpoB gene. The prevalence of ß-hemolytic streptococci was also identified and compared between groups. RESULTS: Forty-four pharyngitis patients and 31 asymptomatic controls were included. F. necrophorum was identified using PCR in 6 (13.6%) pharyngitis cases and 2 (6.5%) controls, with no significant difference (p = 0.457). The median bacterial load of F. necrophorum identified with real-time PCR was significantly higher in pharyngitis cases than in controls (p = 0.046). Patients with a high Centor Score tended to have a higher bacterial load than those with a low Centor Score and controls. In cases of pharyngitis, the prevalence of F. necrophorum was similar to that of Streptococcus pyogenes (F. necrophorum-positive: 6 [13.6%] vs. S. pyogenes-positive: 5 [11.4%], p = 0.99). CONCLUSION: F. necrophorum was similarly prevalent among pharyngitis cases as S. pyogenes in Japan. The association of higher F. necrophorum bacterial load with symptomatic pharyngitis in accordance with the previous findings from a different geographical region suggests that F. necrophorum is an important causative agent of bacterial pharyngitis.

Fever of unknown origin in the outpatient setting: A retrospective analysis of 30 cases of familial Mediterranean fever.

BACKGROUND: In Japan, familial Mediterranean fever (FMF) is a rare cause of fever of unknown origin (FUO). However, we experienced an extraordinary number of FMF cases over 3 years. This suggests that many patients with FMF remain misdiagnosed in Japan. This study examines the clinical picture of FMF to assist Japanese clinicians in daily practice dealing with FUO. PATIENTS AND METHODS: Three years of medical records were reviewed, and 38 patients with FMF or suspected FMF were collected from our patient database. We applied the Tel-Hashomer criteria to those patients. RESULTS: Of the 38 patients, 30 were classified as having FMF in this investigation. The mean patient age was 27.8 years. MEFV gene mutations were detected in 14 patients. Three cases were colchicine-resistant. CONCLUSION: Clinicians should recognize the pattern of short, spontaneously resolving attacks of fever with fever-free intervals, especially when they see patients with recurrent FUO in the outpatient setting.

Two Cases of Granulomatous Mastitis Caused by Corynebacterium kroppenstedtii Infection in Nulliparous Young Women with Hyperprolactinemia.

Recently, an association between granulomatous mastitis and local infection with Corynebacterium (C.) kroppenstedtii has been suggested. We herein report two cases of granulomatous mastitis resulting from C. kroppenstedtii infection in nulliparous young women with hyperprolactinemia. Both cases involved nulliparous patients with drug-induced hyperprolactinemia, and both individuals received incision and drainage, after which the pus was sent to our laboratory. Corynebacterium spp. grew on blood agar, and 16S rRNA gene sequencing identified the pathogen as C. kroppenstedtii. In conclusion, lactational changes caused by drug-induced hyperprolactinemia may increase the risk of granulomatous mastitis after C. kroppenstedtii infection.

Autochthonous dengue fever, Tokyo, Japan, 2014.

After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August-September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.

Meningococcemia due to the 2000 Hajj-associated outbreak strain (Serogroup W-135 ST-11) with immunoreactive complications.

We present the first reported case of systemic infection with Neisseria meningitidis serogroup W-135 sequence type (ST)-11 in Japan. A 44-year-old woman presented with high fever, sore throat, and fatigue and was diagnosed with N. meningitidis bacteremia. The causative strain was identified as serogroup W-135 ST-11 by polymerase chain reaction and multilocus sequence typing. Approximately 1 month after treatment, she developed high fever, dyspnea, chest pain, and shoulder pain due to pericarditis, polyarthritis, and tenosynovitis, which are all relatively common immunoreactive complications of W-135 ST-11 meningococcal infections. This causative strain was the same as that responsible for an outbreak of meningitis among Hajj pilgrims in 2000. The strain is now found worldwide because it can attain a high carriage rate and has a long duration of carriage. We suspect that our patient's infection was acquired from an imported chronic carrier.

Value of carotid artery tenderness for the early diagnosis of Takayasu arteritis.

The early diagnosis and treatment of Takayasu arteritis (TA) is crucial to prevent the devastating complications of vascular insufficiency. This report describes a patient with a persistent fever in whom carotid artery tenderness led to a diagnosis of TA. This case suggests that carotid artery tenderness is a useful physical finding that warrants 2-deoxy-2-[Fluorine-18] fluoro-D-glucose positron emission tomography/computed tomography to confirm a diagnosis of early TA.

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes.

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.

Autoimmune polyglandular syndrome type 3 complicated by mineralocorticoid-responsive hyponatremia of the elderly.

We experienced the first case with autoimmune polyglandular syndrome type 3 (anti-thyroid peroxidase antibody-positive hypothyroidism and anti-glutamic acid decarboxylase antibody-positive diabetes) complicated by mineralocorticoid-responsive hyponatremia of the elderly. This case is also a rare slowly progressive insulin-dependent diabetes mellitus (SPIDDM) case, for which the patient has been treated for many years with sulfonylurea or glinide. Our observation also demonstrated that glucose metabolism in autoimmune diabetes such as SPIDDM is influenced by appetite, thyroid function and glucocorticoid effect.

Time of initial appearance of renal symptoms in the course of systemic lupus erythematosus as a prognostic factor for lupus nephritis.

The prognosis of lupus nephritis (LN) was studied retrospectively in two LN categories, LN manifested initially at systemic lupus erythematosus (SLE) onset (I-LN) and LN of delayed manifestation after SLE onset (D-LN), based on a chart review (C) of 154 SLE (85 LN) patients with a mean observation of 20.8 +/- 9.3 years and a questionnaire study (Q) of 125 LN patients outside our hospital with mean observation of 17.6 +/- 9.2 years. In both study groups, half of I-LN patients were relapse-free by Kaplan-Meier analysis after initial therapy, and the relapsed I-LN patients responded to retherapy at higher 5-year relapse-free rates than those of patients receiving initial therapies for D-LN. At last observation, a higher frequency of prolonged remission was shown in I-LN compared with D-LN patients (C: 22/31, 71% versus 14/49, 29%, P < 0.01; Q: 65/89, 73% versus 11/33, 33% P < 0.01) and also a higher frequency of irreversible renal damage in D-LN compared with I-LN patients (C: 25/49, 51% versus 2/31, 6%, P < 0.001; Q: 14/33, 42% versus 6/89, 7%, P < 0.001), although class IV pathology was common in patients (C) in both LN categories. Onset time of lupus nephritis in the course of SLE may affect renal prognosis.

[A rare case of the lumbar ectopic kidney in Japanese adult].

In this paper, about the left lumber ectopic kidney of a 87-years-old Japanese woman, we observed the size of her kidney, the form of her renal hilum, and the form of her calicopelvic system. In addition, we measured the index of cortex and medulla (C/M), and examined the difference between the lumber ectopic and the normal kidney. There was no significant difference in the size (length, width, thickness, weight), without the external form was the distorted oval of lumber ectopic kidney. The renal hilum was divided into the upper and lower parts by the septum consisted of the parenchyma of kidney. In the calicopelvic system of the left lumber ectopic kidney, an obstructive distension due to the oppression by branch of the renal vein was observed in the superior minor renal calices. It seemed that it was Fraley's syndrome. From the viewpoint of C/M in the lumber ectopic kidney, it was suggested that there was no difference in the renal function, because the C/M was within a normal range.