Internal Medicine
Online ISSN : 1349-7235
Print ISSN : 0918-2918
ISSN-L : 0918-2918
Volume 59 , Issue 3
Showing 1-30 articles out of 30 articles from the selected issue
REVIEW ARTICLE
  • Yuichi Saito, Yoshio Kobayashi
    2020 Volume 59 Issue 3 Pages 311-321
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    Percutaneous coronary intervention (PCI) has become a standard-of-care procedure in the setting of angina or acute coronary syndrome. Antithrombotic therapy is the cornerstone of pharmacological treatment aimed at preventing ischemic events following PCI. Dual antiplatelet therapy as the combination of aspirin and P2Y12 inhibitor has been proven to decrease stent-related thrombotic risks. However, the optimal duration of dual antiplatelet therapy, an appropriate P2Y12 inhibitor, and the choice of aspirin versus P2Y12 inhibitor as single antiplatelet therapy remain controversial. Furthermore, the combined use of oral anticoagulation in addition to antiplatelet therapy is a complex issue in clinical practice, such as in patients with atrial fibrillation. The key challenge concerning the optimal antithrombotic regimen is ensuring a balance between protection against thrombotic events and against excessive increases in bleeding risk. In this review article, we summarize the current evidence concerning antithrombotic therapy in patients with coronary artery disease undergoing PCI.

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ORIGINAL ARTICLES
  • Tetsuya Akaishi, Toru Nakano, Tomomi Machida, Michiaki Abe, Shin Takay ...
    2020 Volume 59 Issue 3 Pages 323-328
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    Objective The definite diagnosis of esophageal achalasia is established using manometry, which is performed in patients with suspected achalasia based on the findings of screening examinations, such as upper gastrointestinal endoscopy, chest computed tomography (CT), or a barium swallow test. However, the exact values of test characteristics in these supportive diagnostic examinations remain unclear.

    Methods We estimated the sensitivity and specificity of characteristic findings in the supportive diagnostic examinations for achalasia by comparing the data of a large number of achalasia patients and others with digestive symptoms.

    Patients Achalasia patients (n=119) and non-achalasia patients with suspected achalasia and repeated feelings of chest discomfort (n=37) who were treated in a single university hospital.

    Results Characteristic findings on chest CT (i.e., dilated esophagus, air-fluid level formation) and barium swallow tests were observed in more than 80% of achalasia patients but in less than 10% of non-achalasia patients. In contrast, conventional characteristic findings of upper gastrointestinal endoscopy (i.e., intra-esophageal food debris, feeling of resistance at the esophagogastric junction) were seen in only 40-70% of achalasia patients. In particular, the feeling of resistance at the esophagogastric junction was observed by the examiner in only 30-50% of patients.

    Conclusion Intra-esophageal food debris or resistance at the esophagogastric junction on upper gastrointestinal endoscopy will be positive in only about half of patients with achalasia. Other supportive diagnostic examinations, such as chest CT or barium fluoroscopy, should therefore be included in order to avoid overlooking the disease.

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  • Norio Akuta, Yusuke Kawamura, Shunichiro Fujiyama, Hitomi Sezaki, Tets ...
    2020 Volume 59 Issue 3 Pages 329-338
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: September 18, 2019
    JOURNALS OPEN ACCESS

    Objective The correlation between the insulin secretion levels and the risk of hepatocarcinogenesis is clinically important. The aim of the present study was to determine the effects of various clinical parameters on C-peptide (CPR) levels in patients with non-alcoholic fatty liver disease (NAFLD).

    Methods In this retrospective cohort study, the effects of clinical parameters on insulin resistance (HOMA-IR) and insulin secretion levels (HOMA-β and fasting CPR) were investigated.

    Patients A total of 244 Japanese patients with histopathologically confirmed NAFLD were evaluated. Of these, 77 underwent the meal tolerance test (MTT) to evaluate the association of various clinical parameters with the CPR levels at 120 minutes.

    Results A multivariate analysis identified fasting plasma glucose (FPG) (≥110 mg/dL), aspartate aminotransferase (≥1.0×ULN IU/L), and a large waist circumference as independent predictors of insulin resistance (HOMA-IR ≥2.5) or high fasting CPR levels. Significant parameters for a low insulin secretion capacity (HOMA-β <30%) were not detected, except for the parameters mentioned in the diagnostic criteria of diabetes mellitus. Regarding the MTT, the CPR levels at 120 minutes were significantly higher in patients with fibrosis stage 3-4 than in those with stage 0-2. Body composition and genetic variation did not affect the CPR levels at 120 minutes. A multivariate analysis identified fibrosis stage (3-4), hyperuricemia, FPG (≥110 mg/dL), and procollagen III peptide (>1.0 U/mL) as independent predictors of high CPR levels at 120 minutes.

    Conclusion The present study showed that high plasma glucose levels and severe liver fibrosis stage influence insulin secretion levels in Japanese patients with NAFLD. Conservation of delayed insulin secretion levels was confirmed in patients with severe liver fibrosis.

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  • Nao Okamoto, Toru Kubo, Yasuteru Nakashima, Yuri Ochi, Asa Takahashi, ...
    2020 Volume 59 Issue 3 Pages 339-343
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    Objective Transthyretin amyloidosis, particularly wild-type transthyretin amyloid cardiomyopathy (ATTRwt), has been recognized as an important cause of morbidity and mortality in the aging population. However, it is difficult to manage heart failure itself in patients with cardiac amyloidosis.

    Methods We herein report the management of heart failure in an elderly patient with severe heart failure due to ATTRwt. We also review the clinical situation in an additional seven patients with cardiac amyloidosis who were administered pimobendan in our hospital.

    Results We treated a 71-year-old man with refractory heart failure due to ATTRwt. He was expected to be dependent on dobutamine infusion. We administered pimobendan and successfully improved his symptoms and hemodynamic status to allow his discharge from the hospital. An additional retrospective investigation observed that there were eight patients with ATTR amyloidosis who were administered pimobendan. Although all of the patients at the time of administration of pimobendan were NYHA class III or IV with repeated hospitalization for heart failure, pimobendan seemed to be effective for improving symptoms and enabling patients to be discharged and receive outpatient medical care. Furthermore, focusing on the changes in some biomarkers, we found that the brain natriuretic peptide and estimated glomerular filtration rate values improved after the administration of pimobendan in 5 consecutive patients for whom data were available without additional treatment (p=0.018 and 0.051, respectively).

    Conclusion In clinical practice, pimobendan seems to have beneficial effects in heart failure management for improving physical activities and the quality of life in patients with transthyretin cardiac amyloidosis.

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  • Shogo Yamamoto, Daisuke Koyama, Ryo Igarashi, Takumi Maki, Hiroyuki Mi ...
    2020 Volume 59 Issue 3 Pages 345-355
    Published: February 01, 2020
    Released: February 01, 2020
    JOURNALS OPEN ACCESS

    Objective To prolong the health expectancy, it is important to prevent age-related diseases, such as osteoporosis and cerebrovascular disease, which are major causes of a bedridden state. Early predictable biomarkers for these diseases are urgently required in the clinical setting. Three members of the fibroblast growth factor (FGF) family - FGF19, FGF21, and FGF23 - are designated as endocrine FGFs and play crucial roles in various metabolic processes. We tried to clarify the clinical utility of endocrine FGFs as biomarkers for age-related diseases in elderly patients.

    Methods We examined the serum endocrine FGF levels and analyzed their association with various clinical parameters in 73 outpatients >60 years old as a single-center cross-sectional study.

    Results In a multivariable linear regression analysis, FGF19 was associated with ALT, a history of cardiovascular disease, and medication with active vitamin D3. FGF21 was associated with the estimated glomerular filtration rate (eGFR), triglyceride level, and hypertension. FGF23 was associated with the eGFR and the serum levels of 1,25-dihydroxy vitamin D3 and TRACP5b. In addition, a receiver operating characteristics analysis revealed that the measurement of FGF21 and FGF23 was useful for detecting chronic kidney disease (CKD) and its complications, including cardiovascular disease and metabolic bone disorder.

    Conclusion The measurement of FGF21 and FGF23 may be useful for evaluating CKD and its complications. Using serum endocrine FGFs as biomarkers for age-related conditions may help prevent elderly patients from entering a bedridden state.

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  • Naro Ohashi, Taro Aoki, Takashi Matsuyama, Sayaka Ishigaki, Shinsuke I ...
    2020 Volume 59 Issue 3 Pages 357-364
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: September 18, 2019
    JOURNALS OPEN ACCESS
    Supplementary material

    Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them in CKD patients.

    Methods We recruited 41 biopsy-proven patients diagnosed with IgA nephropathy (IgAN) in 31, membranous nephropathy (MN) in 5, and tubulointerstitial nephritis (TIN) in 5. The patients taking RAS blockers were excluded.

    Results The urinary albumin levels in MN patients were significantly higher and those in TIN patients significantly lower than in IgAN patients, and the urinary AGT levels in the MN and TIN patients were significantly higher than those in IgAN patients. Conversely, the urinary AGT-to-urinary albumin (urinary AGT/Alb) ratios were the same for IgAN and MN patients, and those of TIN patients were significantly higher than those of IgAN and MN patients. A multiple linear regression analysis revealed that the urinary AGT/Alb ratios had a significant positive association with IgAN and TIN after adjustments (β=0.75, and p<0.01).

    Conclusion These data suggest that the origins of urinary AGT may differ according to the etiology of renal damage [i.e. glomerular damage (such as IgAN and MN) or tubulointerstitial damage (such as TIN)], and a higher urinary AGT/Alb ratio, as in TIN, may reflect AGT production in the kidney.

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CASE REPORTS
  • Nobuhiko Ogasawara, Satoshi Saitoh, Hideyuki Denpou, Keiichi Kinowaki, ...
    2020 Volume 59 Issue 3 Pages 365-372
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 17, 2019
    JOURNALS OPEN ACCESS

    We herein report a 48-year-old healthy woman who visited our hospital to investigate a 25-mm space-occupying lesion in the liver. The tumor was irregularly shaped and exhibited heterogeneous enhancement on dynamic computed tomography (CT). Whole-body positron emission tomography-CT showed an abnormal fluorodeoxyglucose uptake in the liver tumor, with a maximum standardized uptake value of 12.82. During the ensuing three months, the tumor grew rapidly and the serum alpha-fetoprotein levels also rose; partial hepatectomy was therefore performed. Microscopic findings revealed a moderately-to-poorly differentiated hepatocellular carcinoma in the normal liver.

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  • Hiroyuki Nakamura, Ayano Utsunomiya, Yuriko Ishida, Tetsuya Horita
    2020 Volume 59 Issue 3 Pages 373-376
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: September 18, 2019
    JOURNALS OPEN ACCESS

    A 48-year-old man was brought to our emergency room with acute abdominal pain and systemic edema, indicating acute circulatory failure with lactic acidosis. Furosemide treatment paradoxically worsened the systemic edema and induced confusion. He had no drinking history but hardly ate legumes or meats containing thiamine. Administration of fursultiamine dramatically improved the symptoms and subsequently caused pulmonary edema. Thiamine deficiency may occur in nondrinkers with an unbalanced diet. In this condition, diuretic therapy can worsen the symptoms before thiamine supplementation by promoting the flushing of water-soluble vitamins but is needed for the management of secondary pulmonary edema after thiamine replenishment.

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  • Daisuke Yakabe, Shouji Matsushima, Saori Uchino, Kisho Ohtani, Tomomi ...
    2020 Volume 59 Issue 3 Pages 377-381
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 24, 2019
    JOURNALS OPEN ACCESS

    A 44-year-old man was admitted to our hospital due to heart failure. Transthoracic echocardiography demonstrated global hypokinesis with an ejection fraction of 25%, prominent trabeculation and deep intertrabecular recesses, and apical aneurysm with multiple thrombi (10×13 mm in the inferior wall, 15×8 mm in the anterior wall). Cardiac magnetic resonance imaging showed an increased ratio of noncompacted (NC) to compacted (C) myocardium (NC/C ratio >2.3) and apical aneurysm. Coronary angiography revealed no significant stenosis. He was therefore diagnosed with left ventricular noncompaction complicated by apical aneurysm. Four weeks after starting anticoagulation, the multiple apical thrombi disappeared without clinical signs of embolism.

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  • Daisuke Katoh, Hiroshi Yoshino, Kayoko Ikehara, Naoki Kumashiro, Hiros ...
    2020 Volume 59 Issue 3 Pages 383-388
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: September 26, 2019
    JOURNALS OPEN ACCESS

    A patient with underlying Hashimoto's thyroiditis developed amiodarone-induced thyrotoxicosis type 1 that was successfully treated using methimazole in combination with potassium iodide. A 35-year-old woman admitted for perinatal care of twin-to-twin transfusion syndrome was given amiodarone for 7 days for paroxysmal ventricular contraction following pulseless ventricular tachycardia 1 day after delivery. She developed thyrotoxicosis one month after the discontinuation of amiodarone therapy and was negative for thyroid-stimulating hormone receptor antibody. An increased peak velocity of the superior thyroid artery suggested amiodarone-induced thyrotoxicosis type 1. Her thyroid function recovered after combination therapy with methimazole and potassium iodide.

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  • Atsuko Uehara, Tomo Suzuki, Yutaro Yamamoto, Masataka Hasegawa, Kenich ...
    2020 Volume 59 Issue 3 Pages 389-394
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    A 77-year-old man with a history of hypertension, prostate hyperplasia, and urolithiasis was admitted for acute kidney injury caused by hypercalcemia. Neck ultrasonography showed a large cyst adjacent to the right lower thyroid lobe. Although a 99mtechnetium sestamibi scan was negative, an extremely high intracystic intact parathyroid hormone level suggested that the cyst had a parathyroid origin and that a functional parathyroid cyst was present. Immunohistochemical staining for the calcium-sensing receptor (CaSR) after right lower parathyroidectomy revealed CaSR-positive cells lining the cyst, indicating that the functional parathyroid cyst had originated from the hemorrhagic degeneration of a parathyroid adenoma.

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  • Tsuyoshi Yoshizawa, Kenya Yamaguchi, Nozomu Kawata, Hitomi Ryuzaki, Ma ...
    2020 Volume 59 Issue 3 Pages 395-399
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 17, 2019
    JOURNALS OPEN ACCESS

    We analyzed the ERG gene status using fluorescence in situ hybridization (FISH) in two chemotherapy-naïve cases with metastatic castration-resistant prostate cancer (mCRPC) in which abiraterone demonstrated a long-term durable complete response. FISH identified Class 1 Edel and Class 2+ Edel in case 1, and Class 1 Edel in case 2. Our experience suggests that abiraterone may be effective in cases with mCRPC and ERG gene abnormalities, particularly Class 2+ Edel or Class 1 Edel. This is the first report of two cases with mCRPC that simultaneously investigated the ERG gene status and clinical aspects, including image evaluations and pathology.

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  • Mayuko Kori, Nobuyasu Awano, Minoru Inomata, Naoyuki Kuse, Mari Tone, ...
    2020 Volume 59 Issue 3 Pages 401-408
    Published: February 01, 2020
    Released: February 01, 2020
    JOURNALS OPEN ACCESS

    We herein report a case of anti-MDA5 antibody-positive, clinically amyopathic dermatomyositis complicated by unilateral interstitial lung disease (ILD) in a 78-year-old man with a history of left lung tumor resection. He was admitted due to a persistent fever and abnormal right pulmonary opacity. A transbronchial lung cryobiopsy revealed pulmonary fibrosis, and combined immunosuppressive therapy was initiated. Findings from multiple evaluations, including dynamic breathing magnetic resonance imaging, supported decreased perfusion, ventilation, and mobility of the left lung as etiological factors of unilateral lung ILD. When patients present with laterality of such findings, clinicians should be aware that atypical imaging findings may be observed.

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  • Tetsuo Shimizu, Yoshiko Nakagawa, Yuko Iida, Kentaro Hayashi, Yoshihir ...
    2020 Volume 59 Issue 3 Pages 409-414
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    We herein report a case of refractory exogenous lipoid pneumonia that was successfully attributed to vegetable oil through a lipidomic analysis of bronchoalveolar lavage fluid (BALF). As a 25-year-old woman diagnosed with lipoid pneumonia experienced repeated exacerbations and improvement, we performed a BALF lipidomic analysis. The major lipid components were oleic acid, linoleic acid, and α-linolenic acid, which are constituents of vegetable oil. She stopped consuming any vegetable oil and has since experienced no instances of lipoid pneumonia relapse. A lipidomic analysis appears to be useful for identifying causative lipids, since patients with lipoid pneumonia are sometimes unaware of aspiration episodes.

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  • Takeshi Saraya, Masachika Fujiwara, Takuma Yokoyama, Saori Takata, Ter ...
    2020 Volume 59 Issue 3 Pages 415-419
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    A 60-year-old woman with a 20-year history of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis visited our hospital due to productive cough and a low-grade fever for several weeks. Thoracic computed tomography demonstrated scattered tiny nodules, patchy consolidation, ground glass opacities, and thickening interlobular septa. On video-assisted thoracic surgery, those abnormalities were found to correspond to the accumulation of hemosiderin-laden alveolar macrophages (AMs) in the alveolar spaces and alveolar septa due to MPO-ANCA vasculitis. The radiological findings persisted for a further two years, indicating the possibility of persistent vasculitis in the lung or evidence of incomplete clearance of hemosiderin-laden AMs.

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  • Takashi Ishiguro, Shuko Hirota, Yasuhito Kobayashi, Kenji Takano, Yoic ...
    2020 Volume 59 Issue 3 Pages 421-424
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    A 70-year-old woman was admitted to our hospital for dyspnea and a fever of 2 weeks duration. Chest imaging showed bilateral infiltration, and a rapid diagnostic test for influenza virus, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Legionella spp. was negative. She was intubated and mechanically ventilated and underwent bronchoalveolar lavage. Bronchoalveolar lavage fluid yielded no significant pathogens, and the multiplex polymerase chain reaction test was positive only for human bocavirus. Specific antibodies against significant pathogens were not increased in paired sera, so we diagnosed her with primary human bocavirus pneumonia.

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  • Yuki Iijima, Tomoya Tateishi, Kimitake Tsuchiya, Yuki Sumi, Takumi Aka ...
    2020 Volume 59 Issue 3 Pages 425-428
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 24, 2019
    JOURNALS OPEN ACCESS

    A 61-year-old man was referred to our hospital with dyspnea and an abnormal lung shadow. His occupational history, pathological findings, and an elemental analysis led to a definitive diagnosis of pneumoconiosis induced by titanium grindings. The patient experienced gradual improvement solely by avoiding titanium grindings. Titanium-induced lung disease is very rare, and most of these cases are caused by inhalation of titanium dioxide (TiO2), which is included in a wide range of commercially available products, such as paints, pigments, and cosmetics. However, industrial workers can also develop lung diseases due to the inhalation of metallic titanium materials during metal grinding.

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  • Eri Iwami, Fumimaro Ito, Kotaro Sasahara, Aoi Kuroda, Tatsu Matsuzaki, ...
    2020 Volume 59 Issue 3 Pages 429-433
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 17, 2019
    JOURNALS OPEN ACCESS

    A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.

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  • Yuki Fukami, Haruki Koike, Masahiro Iijima, Junichirou Hagita, Hisayos ...
    2020 Volume 59 Issue 3 Pages 435-438
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    We herein report the case of a 67-year-old man who presented with the acute onset of limb weakness. Brain magnetic resonance imaging revealed multiple abnormal-signal-intensity lesions. Steroids were administered, and the patient initially responded. Nerve conduction testing findings were consistent with demyelinating polyneuropathy. A sural nerve biopsy specimen revealed fascicles with extensive onion-bulb formation. Although skin and sural nerve biopsies showed no atypical cellular infiltration, the histopathological diagnosis of intravascular large B-cell lymphoma was obtained by a brain biopsy. The neuropathy in this patient may be attributed to a demyelinating process independent of ischemic damage by lymphoma.

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  • Natsuki Shima, Yoichiro Akiyama, Shotaro Yamamoto, Ayako Kokuzawa, Kat ...
    2020 Volume 59 Issue 3 Pages 439-443
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 07, 2019
    JOURNALS OPEN ACCESS

    A 48-year-old woman with severe pain and numbness of her right leg and foot was admitted to our hospital. She had never smoked and had little exposure to passive smoking. Initially, polyarteritis nodosa with anti-phospholipid antibodies was considered. Combination therapy with methylprednisolone pulse therapy, intravenous cyclophosphamide pulse therapy, vasodilators, antiplatelet agents, and anticoagulants was not effective. Vasculopathy was progressive, and she presented with gangrene of the toes. She required amputation of her right leg. The pathological findings of the amputated leg revealed thromboangiitis obliterans (TAO). TAO should be considered even in non-smoking women. Non-response to immunosuppressant and anticoagulant therapies may be a clue to the diagnosis of TAO.

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  • Masahiro Kaneko, Naoto Ishimaru, Takahiro Nakajima, Yohei Kanzawa, Hir ...
    2020 Volume 59 Issue 3 Pages 445-451
    Published: February 01, 2020
    Released: February 01, 2020
    [Advance publication] Released: October 24, 2019
    JOURNALS OPEN ACCESS

    Japanese spotted fever (JSF) is an uncommon but potentially fatal infection transmitted by tick bites. We herein report a fulminant case of JSF infection that occurred in an immunocompetent adult that was complicated by disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis (HLH). We discuss the difficulty in making the diagnosis and identifying the complication of HLH in our patient. HLH is a rare complication of rickettsiosis, and this is the first reported case in English of JSF complicated by HLH in an immunocompetent adult. Secondary HLH caused by rickettsiosis requires a different treatment from primary HLH. Rickettsiosis must therefore be considered in patients with HLH.

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