[AN ADULT CASE OF PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, AND ADENITIS (PFAPA) SYNDROME DEVELOPED IN CHILDHOOD AND DIAGNOSED AFTER PROGRESS MORE THAN 30 YEARS].

We report an adult case of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, who had a tonsillectomy at 10 years old and relapsed later. An early 40's-year-old man had been suffering from recurrent fever attack once in 1-2 months during childhood. He was accompanied by fever which was persist for several days, aphthous stomatitis, tongued tonsillitis with moss, pharyngitis, and submandibular lymphadenitis with tenderness. He was not doing well during fare-up. At the time of admission, CRP level was 12.5mg/dl and the remarkably increased expression of CD64 on neutrophils was found. Bacterial infections and collagen diseases were excluded by the several examinations. We suspected PFAPA syndrome, and treated with cimetidine, but cimetidine was not effective. At the time of flare up, administration of prednisolone was remarkably effective. We diagnosed PFAPA syndrome on the basis of clinical courses. Genetic analysis of responsible gene of familial Mediterranean fever, MEFV showed E148Q heterozygous mutation in exon 2.Since an adult case of PFAPA syndrome is likely to be made misunderstanding for infectious recurrent pharyngitis, it is important to note that we should consider PFAPA syndrome as a differential diagnosis when we meet with the adult patient of recurrent fever.

Adult-onset Still's disease with disseminated intravascular coagulation and hemophagocytic syndrome: a case report.

BACKGROUND: Adult-onset Still's disease is a rare inflammatory condition of unknown origin characterized by high spiking fever, arthralgia, arthritis, myalgia, salmon-colored evanescent rash, and hepatosplenomegaly. The diagnosis of adult-onset Still's disease requires the exclusion of other possible disorders because it lacks specific clinical and histopathological findings. Adult-onset Still's disease rarely become fatal due to visceral involvements such as disseminated intravascular coagulation. CASE PRESENTATION: A 22-year-old Chinese female presented to our medical center with high spiking fever for one week, myalgia for two weeks, and arthralgia and pink maculopapular rash for four weeks. She developed disseminated intravascular coagulation on the fourth day after admission. There was no other explanation for the fever and rash, including infection, malignancy, and collagenosis. Together, the high spiking fever, salmon-colored rash, splenomegaly, and excess hepatic enzyme, indicated adult-onset Still's disease based on the Yamaguchi criteria. Therefore, prednisolone therapy was initiated. The combination of nafamostat mesilate and prednisolone therapies caused a rapid reduction in the fever and rash. The inflammatory markers decreased immediately, and disseminated intravascular coagulation improved. Her symptoms resolved with low-dose prednisolone treatment, and she was monitored thereafter at our outpatient clinic. CONCLUSION: The previous use of nonsteroidal anti-inflammatory drugs could have caused disseminated intravascular coagulation in this patient with adult-onset Still's disease. We propose that physicians should consider the possibility of disseminated intravascular coagulation as a complication during the course of adult-onset Still's disease and suggest that prednisolone therapy should be initiated in the early stages of adult-onset Still's disease.

[A fatal case of septicemia by serotype A:3 Pasteurella multocida in human: review of 14 septic cases in Japan].

We report a case of systemic inflammatory response syndrome (SIRS) due to septicemia by Pasteurella multocida (P. multocida) who died three days after on admission. A few cases of septicemia by P. multocida were previously reported. In particular, capsular serotype analysis and somatic serotype analysis of P. multocida in human is very rare. Serotype A:3 P. multocida was identified in a diabetic patient with chronic obstructive pulmonary disease (COPD). There was high possibility that the isolate has been transmitted from an indoor companion dog since the patient had had close contact with the dog for one month. Here we discuss our case and 13 human cases of septicemia by P. multocida reported in Japan. Four cases from dogs and eleven cases from cats were included in these cases. The mortality rate of septicemia by P. multocida was 21.4% (3/14 cases). Two out of three cases died were diabetic.

Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study.

UNLABELLED: Efficacy of first-line gefitinib for elderly epidermal growth factor receptor mutated patients with lung adenocarcinoma is uncertain. This study was aimed to investigate efficacy of gefitinib for such population. The primary endpoint was response rate (RR) and at least 12 cases were needed. Overall RR was 59% (95% confidence interval, 33%-81%) and first-line gefitinib was effective for elderly patients. INTRODUCTION: Feasibility of gefitinib therapy in elderly patients with non-small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%). CONCLUSION: First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.

A pregnant Japanese woman returning from Africa with recurrent fevers.

Certain clinical aspects of vivax malaria are no longer defined as benign. We present a case of vivax malaria with three relapses in a pregnant Japanese woman who had returned to Japan from the Comoros Islands in East Africa. Data on the successful delivery, examination of Duffy-blood group antigen, and microscopic findings of growing stages of Plasmodium vivax are thought to be of considerable interest.

[A case of acute eosinophilic pneumonia with a disassociation between the KL-6 level and SP-A and SP-D levels in the serum and BAL fluid].

A 45-year-old Japanese electrical engineer was admitted to our department of internal medicine on August 12, 2003, because of a sudden high fever and severe hypoxic respiratory failure. At a barbecue with his family on August 3 beside a nearby river, he had been exposed to the smoke. From August 4 to 11, he had suffered fatigue, fever, dry cough and progressive dyspnea. On admission, his SpO2 was 84%, and computed tomography scanning showed patchy ground glass opacity, thickened bronchial walls, and bilateral pleural effusions. The eosinophil count in the bronchoalveolar lavage fluid (BALF) was increased to 52.4%. Noticeably, the KL-6, SP-A and SP-D levels in the serum were elevated to 197 U/ml, 188 ng/ml and 137 ng/ml, and their levels in BALF had also increased to 225 U/ml, 890 ng/ml and 1110 ng/ml, respectively. The lymphocyte stimulation test was negative, and the cultures of blood and BALF did not grow any pathogens. The patient had smoked 1 pack of per cigarettes day for 25 years and showed no sign of atopic illness. Acute eosinophilic pneumonia (AEP) was diagnosed, and responded dramatically to treatment with oxygen and corticosteroids. The dissociation between the normal KL-6 levels and the elevated SP-A and SP-D levels in the serum and BAL fluid may play an important role in cases of AEP.

Methotrexate stimulates lung epithelial cells to release inflammatory cell chemotactic activities.

Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemotactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B(4) receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB(4) receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) antibodies. ECA was attenuated by LTB(4) receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB(4) from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate.

[Four cases of Klebsiella pneumonia].

Typical Klebsiella pneumonia with mucous sputum is known as an opportunistic nosocomial infection. However, computed tomographic study of limiting in Klebsiella pneumonia is rare. We report three types of chest computed tomography (CT) findings for Klebsiella pneumonia. Case 1 shows typical lobar pneumonia (Friedlander pneumonia), Cases 2 and 3 show acute bronchopneumonia with subclinical aspiration, and Case 4, chronic Klebsiella pneumonia with typical cavitary lung abscesses. Of these four cases of Klebsiella pneumonia, three developed in the right lung, as determined radiologically, but esophagogastroduodenoscopy indicated that the lesions of Case 3 had developed in the left lingula and upper lobe.

Small-intestinal sarcomatoid carcinoma with superior vena cava syndrome.

A 56-year-old man was hospitalized because of swelling of the right upper extremity and anemia. A diagnosis of superior vena cava (SVC) syndrome caused by lymphogenous metastasis was made after chest computed tomography (CT) scan and biopsy of cervical lymph nodes were carried out. Standard examinations, such as abdominal CT scan and endoscopies of the upper and lower gastrointestinal tract, failed to find the primary lesion. However, selective angiography of the superior mesenteric artery (SMA) showed a clear stain of bleeding vessels in the small intestine. Laparotomy was performed, and immunohistochemical findings revealed sarcomatoid carcinoma in the small intestine (a rarely seen neoplasm). This aggressive carcinoma, which showed negative reactivity with CD34, CD117 (c-kit), and S-100 was clearly distinguished from other mesenchymal tumors, such as malignant gastrointestinal stromal tumor (GIST) and malignant fibrous histiocytoma (MFH).

Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy).

The role of systemic chemotherapy and optimal regimen in thymic carcinoma remains uncertain. We evaluated the clinical responsiveness of ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) chemotherapy for advanced thymic carcinoma that have distant metastatic or unresectable lesions. From 1996 to 2000, we treated eight cases of thymic carcinoma. According to the classification by Masaoka et al., the clinical stage in one case was IVa, whereas the others were IVb. Histologic subtypes were as follows: four cases were squamous cell carcinoma, two cases were undifferentiated, and two were small-cell carcinoma. All patients received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously on day 1, 0.6 mg/m2 of vincristine intravenously on day 3, and 700 mg/m2 of cyclophosphamide intravenously on day 4, ADOC regimen, respectively, at 3- to 4-week intervals. Six patients obtained a partial response after ADOC chemotherapy and the overall clinical response rate was 75%. There were no life-threatening side effects noted. Cisplatin plus VP-16 chemotherapy (PVP) was performed in three cases before the ADOC regimen, but PVP chemotherapy did not show beneficial effects in two patients. Median survival time was 19 months. ADOC chemotherapy appears to have significant activity against thymic carcinoma.

Histamine and serotonin stimulate eotaxin production by a human lung fibroblast cell line.

Histamine and serotonin are important inflammatory mediators in the pathophysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than nonasthmatic control subjects. Eotaxin, a potent eosinophil-specific chemotactic factor, is increased in the lower respiratory tract of allergic patients. Recently, lung fibroblasts have been reported to produce eotaxin and are suggested to be the major cellular source of eotaxin. We postulated that lung fibroblasts might release eotaxin in response to histamine or serotonin. To test this hypothesis, we evaluated the potential of histamine or serotonin to induce the release of eotaxin by the human fetal lung fibroblast cell line, HFL-1. HFL-1 released eotaxin in response to histamine and serotonin in a dose- and time-dependent manner (p < 0.05). Histamine or serotonin treatment of HFL-1 augmented the expression of eotaxin mRNA. Eosinophil chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. These findings lead to the hypothesis that lung-fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in allergic disease of the airways.

[An infection with Legionella pneumophila treated with intravenous ciprofloxacin].

A 60-year-old diabetic man who had had a coronary artery bypass graft operation was admitted to Okaya Enrei Hospital because of coughing, high fever and dyspnea. Chest high-resolution computed tomography scans revealed bilateral pleural effusions and left-sided alveolar shadows and ground glass opacity. These infiltrations in the left lung field showed rapid growth. Legionella pneumonia was diagnosed because of a high titer for Legionella pneumophila antigen in the urine. He was treated with 600 mg per day of parenteral ciprofloxacin for two weeks and 10 mg per day of oral prednisolone for the second week, resulting in improvement of the clinical findings.

Chromosomal aberrations in intravascular lymphomatosis.

Intravascular lymphomatosis (IVL) is a unique, disseminated type of malignant lymphoma. However, no detailed comparative study limited to the chromosomal aberrations of IVL has been reported, because IVL is extremely rare and difficult to diagnose while the patient is alive. We present here a case of IVL, and compare its karyotype with those of five cases of previously reported IVL. The accumulation of structural aberrations in chromosomes 1, 6, and 18, especially 1p (4 of 6 cases) and trisomy 18 (4 of 6 cases), were found in our comparative study of the B-cell lineage typical IVL. These chromosomal rearrangements must provide important information regarding the characteristics of cytogenetically associated with the cellular genetics of IVL.

Human bronchial epithelium expresses interleukin-9 receptors and releases neutrophil chemotactic factor.

Growing evidence obtained from human genomic analysis and antigen-challenged transgenic mice suggests that interleukin-9 (IL-9) is a candidate factor in immunoglobulin E (IgE) production and thus is thought to be associated with bronchial inflammation and bronchial hyperresponsiveness (BHR). To evaluate the expression of the IL-9 receptor and its effect on the IL-9 human bronchial cell line BEAS-2B cells, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical investigation, and chemotaxis assay were performed. The components of the IL-9 receptor, consisting of IL-9 receptor alpha (CD129) and IL-2 receptory ((1)132), were expressed on BEAS-2B cells as determined by RT-PCR and flow cytometry. BEAS-2B cells exposed to IL-9 released neutrophil chemotactic activity (NCA) in a time- and dose-dependent manner, and the presence of granulocyte colony-stimulating factor (G-CSF) was also detected. This factor is primarily involved in NCA for the measurement of cytokines and in the inhibition assay of neutrophil chemotaxis. These findings suggest that bronchial epithelial cells may express IL-9 receptors, and that IL-9 may induce airway inflammation through the release of G-CSF from bronchial epithelial cells.