In vitro efficacy of humanized regimen of flomoxef against extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

This study compared the efficacy of flomoxef with other ß-lactam antibiotics against extended-spectrum ß-lactamases (ESBL)-producing bacteria of clinical relevance. First, the prevalence and ß-lactamase genotypes of ESBL-producing strains among Escherichia coli and Klebsiella pneumoniae isolates collected in Japan from 2004 to 2018 were investigated. High MIC90 values (>64 µg/mL) of ceftriaxone, cefepime, and ceftazidime and low MIC90 values (≤0.06-2 µg/mL) of flomoxef, cefmetazole, and meropenem against both species were observed. Second, a chemostat model was used to analyze the efficacy of humanized regimens of three oxacephem/cephamycin antibiotics (flomoxef, cefmetazole, cefoxitin) and two other antibiotics (meropenem and piperacillin/tazobactam) in suppressing the growth of five ESBL-producing E. coli and two K. pneumoniae strains. Flomoxef, piperacillin/tazobactam, and meropenem showed good bactericidal effects with >4 log10 CFU/mL reduction without bacterial regrowth at 24 h even when the MIC of test isolates was >MIC90. Cefmetazole and cefoxitin resulted in regrowth of test isolates with MIC ≥MIC90 at 24 h. Cefmetazole, cefoxitin, flomoxef, and meropenem showed increased MICs for regrown samples. A clear relationship between the proportion of time that the free drug concentration exceeded the MIC (%fT>MIC) and antibiotic efficacy was found for flomoxef, cefoxitin, and cefmetazole, and flomoxef had the highest %fT>MIC, whereas discrepancies between Clinical and Laboratory Standards Institute breakpoint and bactericidal activity were observed for cefmetazole. Flomoxef was effective in preventing the growth of all ESBL-producing strains, even those with an MIC eight times the MIC90. Thus, flomoxef may be a good alternative to meropenem in context of carbapenems sparing stewardship.

First Japanese case of disseminated blastomycosis imported from North America: A case report.

Blastomycosis is a fungal infectious disease that can occur in both immunocompromised and immunocompetent populations endemic in North America, with no previous reports in Japan. A 26-year-old Japanese female patient with no relevant medical history presented intermittent left back pain and an abnormal shadow in the left upper lung field eight months ago at a local clinic. She was referred to our hospital for further evaluation and treatment. The patient currently lives in Japan, but until two years ago had spent several years in New York, Vermont and California. Chest computed tomography revealed a 30 mm mass with a cavity in the left pulmonary apex. The specimens obtained by transbronchial biopsy showed periodic acid-Schiff stain (PAS)-positive and Grocott-positive yeast-like fungi scattered among the granulomas, with no malignant findings, and the initial pathology did not lead to a definitive diagnosis. She was empirically started on fluconazole because of onset of multiple subcutaneous abscesses and was referred to the Medical Mycology Research Center. Although antibody tests could not diagnose the disease, blastomycosis was suspected based on the pathology of the skin and lung tissue at the Medical Mycology Research Center, and Blastomyces dermatitidis was identified by ITS analysis of the rRNA region. Her symptoms and CT findings gradually improved with fluconazole. We reported the first Japanese case of blastomycosis with pulmonary and cutaneous involvement in Japan. As the number of overseas travelers is expected to continue increasing, we would like to emphasize the importance of travel history interviews and information of blastomycosis.

Two cases of novel coronavirus infection (COVID-19) with transient viral elevation using semi-quantitative real-time reverse transcription PCR and symptom relapse after completion of 10 days of favipiravir treatment.

The coronavirus disease of 2019 (COVID-19), which began in Wuhan, China, at the end of 2019, is spreading around the world and causing many deaths, mainly from pneumonia. Currently, there are no specific drugs to treat COVID-19, and existing antiviral drugs are being used as an alternative. One of these is favipiravir, a new type of influenza drug. However, its efficacy, dosage, and duration of administration are still under study. In this case study, we administered favipiravir to patients with COVID-19 and determined the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pathogen, using semi-quantitative real-time reverse transcription PCR in sputum samples. We report on two patients in whom the viral load increased again after completion of 10 days of favipiravir treatment and a transient relapse of symptoms was observed.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Human herpesvirus 8-positive multicentric Castleman disease with germinotropic plasmablastic aggregates: Overlapping spectrum of human herpesvirus 8-associated lymphoproliferative disorder.

The diagnosis of human herpesvirus 8 (HHV8)-associated lymphoproliferative disorder (LPD) is challenging because of the rarity and extended spectrum of each entity. A 43-year-old, human immunodeficiency virus seropositive, Japanese man was referred to our department because of persistent fever, generalized lymphadenopathy, jaundice and anasarca. Biopsy of a left axially lymph node demonstrated relatively preserved nodal structure with multicentric Castleman disease (MCD) features. In the germinal center, there were aggregates of HHV8-infected plasmablasts that were diffusely positive for CD38, MUM1/IRF4, LCA, IgM and λ; partially positive for CD30, c-MYC, p53; and negative for CD138, CD20, PAX-5, κ, CD2, CD3 and CD5. A small number of Epstein-Barr virus encoded small RNA (EBER)-positive large cells infiltrated in the outer part of the germinal center and the mantle layer, but the cells copositive for EBER and HHV8 were not evident. We diagnosed the patient as HHV8-positive MCD with germinotropic plasmablastic aggregates, which demonstrated intermediate pathologic features between HHV8-positive MCD and germinotropic lymphoproliferative disorder. The pathogenesis of each HHV8-associated LPD differs in cellular origin, host immune status, cytoplasmic immunoglobulin expression, clonality pattern and EBV infection; however, these factors sometimes overlap and induce extended clinical and pathologic presentations.

Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study.

BACKGROUND: The detection of infectious bacteria in blood culture samples is important for diagnosis and treatment, but this requires 1-2 days at least, and is not adequate as a rapid test. Therefore, we have investigated the diagnostic ability and the optimal cutoff value of procalcitonin (PCT) and C-reactive protein (CRP) for predicting the bacteremias using receiver operating characteristic (ROC) curves and relative cumulative frequency distribution (RCD) curves. METHODS: A case-control study was performed in inpatients (852 subjects: 426 positive cultures and 426 negative cultures) from January 1 to December 31, 2014. We retrospectively investigated their blood culture and blood chemistry findings recorded in this period using electronic medical records. RESULTS: Area under the ROC curve of PCT and CRP were 0.79 and 0.66, respectively. The optimal cutoff values were 0.5 µg/L with a sensitivity of 70% and specificity of 70% for PCT and 50.0 mg/L with a sensitivity of 63% and specificity of 65% for CRP. When the optimal cutoff value was treated as a reference, the odds ratio (OR) was 71.11 and the hazard ratio (HR) was 6.27 for PCT >2.0 µg/L, and the risk of blood culture positivity was markedly elevated. PCT levels were significantly higher in the population with Gram-negative rod (GNR) infections than in the population with Gram-positive coccal (GPC) infections. CONCLUSIONS: The elevation of CRP and PCT were significantly associated with bacteremias. PCT was superior to CRP as a diagnostic indicator for predicting bacteremias, for discriminating bacterial from nonbacterial infections, and for determining bacterial species.

Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient.

Introduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs. Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro. Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs. Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.

Evaluation of potential rabies exposure among Japanese international travelers: A retrospective descriptive study.

BACKGROUND: Although Japan has been a rabies-free country for >50 years, a few cases have been reported among people traveling abroad. This study aimed to investigate animal exposure among Japanese travelers using the Japanese Registry for Infectious Diseases from Abroad (J-RIDA). METHOD: In this retrospective analysis, we examined Japanese overseas travelers with animal exposure, as included the J-RIDA database, reported from October 1, 2017, to October 31, 2019, with a focus on pre-exposure prophylaxis (PrEP) administration and the animals to which the patients were exposed. RESULTS: Among the 322 cases included in the analysis, 19 (5.9%) patients received PrEP and 303 did not. The most common purpose of travel was a non-package tour (n = 175, 54.3%). Most trips (n = 213, 66.1%) were to a single country for <2 weeks. Most patients (n = 286, 87.9%) traveled to countries with a rabies risk. The majority of patients with and without PrEP were injured in rabies-risk countries [n = 270 (89.1%) for non-PrEP and n = 16 (84.2%) for PrEP]. Animals associated with injuries included dogs (55.0%), cats (25.5%), and monkeys (15.5%). Most patients were classified as World Health Organization Category II/III for contact with suspected rabid animals (39.5% and 44.1% for categories II and III, respectively) and had exposure within 5 days of travel. Southeast Asia (n = 180, 55.9%) was the most common region in which travelers were exposed to animals. CONCLUSIONS: Japanese overseas travelers had contact with animals that could possibly transmit the rabies virus, even on short trips. Promoting pre-travel consultation and increasing awareness of the potential for rabies exposure are important for prevention of rabies among Japanese international travelers.

Usefulness of a semi-quantitative procalcitonin test and the A-DROP Japanese prognostic scale for predicting mortality among adults hospitalized with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The solid-phase immunoassay, semi-quantitative procalcitonin (PCT) test (B R A H M S PCT-Q) can be used to rapidly categorize PCT levels into four grades. However, the usefulness of this kit for determining the prognosis of adult patients with community-acquired pneumonia (CAP) is unclear. METHODS: A prospective study was conducted in two Japanese hospitals to evaluate the usefulness of this PCT test in determining the prognosis of adult patients with CAP. The accuracy of the age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scale proposed by the Japanese Respiratory Society for prediction of mortality due to CAP was also investigated. Hospitalized CAP patients (n = 226) were enrolled in the study. Comprehensive examinations were performed to determine PCT and CRP concentrations, disease severity based on the A-DROP, pneumonia severity index (PSI) and confusion, urea, respiratory rate, blood pressure, age ≥65 (CURB-65) scales and the causative pathogens. The usefulness of the biomarkers and prognostic scales for predicting each outcome were then examined. RESULTS: Twenty of the 170 eligible patients died. PCT levels were strongly positively correlated with PSI (ρ = 0.56, P < 0.0001), A-DROP (ρ = 0.61, P < 0.0001) and CURB-65 scores (ρ = 0.58, P < 0.0001). The areas under the receiver operating characteristic curves (95% CI) for prediction of survival, for CRP, PCT, A-DROP, CURB-65, and PSI were 0.54 (0.42-0.67), 0.80 (0.70-0.90), 0.88 (0.82-0.94), 0.88 (0.82-0.94), and 0.89 (0.85-0.94), respectively. The 30-day mortality among patients who were PCT-positive (≥0.5 ng/mL) was significantly higher than that among PCT-negative patients (log-rank test, P < 0.001). CONCLUSIONS: The semi-quantitative PCT test and the A-DROP scale were found to be useful for predicting mortality in adult patients with CAP.

Sarcopenia among people living with HIV and the effect of antiretroviral therapy on body composition.

To investigate the prevalence of sarcopenia among people living with HIV (PLWH) in Japan and analyze the relationship between HIV infection and ART effects on the body composition of Japanese PLWH for more appropriate drug selection and lifestyle guidance. Cross-sectional observational study. We included male patients aged ≥ 60 years whose body composition was measured by InBody 570 body composition analyzer during outpatient visits. Patients were classified by body shape based on body mass index (BMI) and body fat percentage measurements and by tenofovir alafenamide administration. Hidden obesity is a condition wherein the BMI is within the standard range but the body fat percentage is higher than the reference. Patients with low muscle mass and strength were considered to have sarcopenia, whereas those with only low muscle strength were considered to have pre-sarcopenia. In total, 87 patients were included. Based on body shape determined by BMI and body fat percentage, most patients had hidden obesity (40 patients, 46.0%). Sarcopenia was detected in 9 patients (10.3%) and pre-sarcopenia in 14 patients (16.1%). The tenofovir alafenamide (TAF) use group had significantly higher BMI, higher skeletal muscle mass, body fat mass, and skeletal muscle mass index relative to the non-TAF use group. Hidden obesity is a risk for lifestyle diseases. It is important to recognize it based on body composition measurements because it can be missed by BMI measurement alone. Tenofovir alafenamide therapy increases skeletal muscle mass, which may result in the prevention of sarcopenia. To clarify how TAF affects the development of sarcopenia and lifestyle diseases, future studies on a larger cohort are warranted.

The Body Fat Percentage Rather Than the BMI Is Associated with the CD4 Count among HIV Positive Japanese Individuals.

Maintenance of the cluster of differentiation 4 (CD4) positive lymphocyte count (CD4 count) is important for human immunodeficiency virus (HIV) positive individuals. Although a higher body mass index (BMI) is shown to be associated with a higher CD4 count, BMI itself does not reflect body composition. Therefore, we examined the association of body weight, body composition and the CD4 count, and determined the optimal ranges of CD4 count associated factors in Japanese HIV positive individuals. This cross-sectional study included 338 male patients treated with antiretroviral therapy for ≥12 months. Multiple logistic regression analysis was used to identify factors significantly associated with a CD4 count of ≥500 cells (mm3)-1. The cutoff values of factors for a CD4 ≥ 500 cells (mm3)-1 and cardiovascular disease risk were obtained by receiver operating characteristic curves. Age, body fat percentage (BF%), nadir CD4 count, duration of antiretroviral therapy (ART), years since the HIV-positive diagnosis and cholesterol intake showed significant associations with the CD4 count. The cutoff value of BF% for a CD4 ≥ 500 cells (mm3)-1 and lower cardiovascular disease risk were ≥25.1% and ≤25.5%, respectively. The BF%, but not the BMI, was associated with CD4 count. For the management of HIV positive individuals, 25% appears to be the optimal BF% when considering the balance between CD4 count management and cardiovascular disease risk.

Usefulness and Safety of Remote Continuous Glucose Monitoring for a Severe COVID-19 Patient with Diabetes.

Diabetes is associated with mortality and severity of coronavirus disease (COVID-19). Protecting against infection in health care workers at high risk of COVID-19 is critical. This report investigates the usefulness and safety of remote continuous glucose monitoring (CGM) in a patient with diabetes and severe interstitial pneumonia caused by the coronavirus disease. The Dexcom G4 Platinum CGM system® was used to monitor blood glucose (BG) levels from outside the patient's isolation room. Continuous insulin infusion rates and boluses were determined based on the patient's BG levels. Real-time CGM made it possible to track BG trends and prevent dramatic variations in BG, although the rate of insulin infusion changed dynamic. Furthermore, the need for health care workers to enter the isolation room was minimized because the Dexcom G4 Platinum CGM system can evaluate from a distance of up to 6.0 m.

A case of urgent colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient receiving heparin for COVID-19 coagulopathy.

COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.

Development of various arrhythmias and conduction disturbances following corticosteroid therapy for systemic lupus erythematosus with antiphospholipid syndrome.

A 45-year-old Chinese woman with active systemic lupus erythematosus, lupus anticoagulant positive, was admitted to our hospital. Electrocardiography on admission was normal. Though anti-Sjögren's syndrome A (anti SS-A/Ro) antibodies were negative and ultrasound cardiographic findings were normal, she developed various arrhythmias/conduction disturbances shortly after starting corticosteroid. Nearly all were resolved with continuous corticosteroid and aspirin therapy before discharge. Vasculitis, the presence of antiphospholipid antibodies, and platelet aggregation due to corticosteroid were possible mechanisms underlying the arrhythmias/conduction disturbances.

Dengue Virus in Traveler Returning to Japan from the Democratic Republic of the Congo, 2015.

Dengue fever (DF) is a mosquito-borne disease and a significant global public health problem. Although a few serological surveys in the literature suggest endemic DF in many parts of Africa, DF cases in these countries are generally underreported because of the lack of diagnostic testing and systematic surveillance; thus, little is known about the phylogenetic profile of circulating strains. In April 2015, DF was diagnosed in a Japanese national returning from the Democratic Republic of the Congo (DRC). Dengue virus 1 (DENV-1) RNA was detected in the patient's serum sample using real-time reverse transcription PCR. Phylogenetic analysis of the E gene revealed that the detected DENV-1 strain was classified as genotype V and was closely related, with 100% nucleotide identity, to the strain causing the 2013 DF epidemic in Angola, which is located directly south of the DRC. This is the first report to characterize the circulating DENV strain in the DRC, and the findings indicate that the DENV-1 strain causing the 2013 DF epidemic in Angola was also circulating in the DRC in 2015.

Multiple Medium Amoebic Liver Abscesses Successfully Treated with Medication and Comprehensive Percutaneous Catheter Drainage.

Solitary small (<5 cm) amoebic liver abscesses in the right lobe are generally treated using medication alone, while large abscesses are typically treated via a combination of medication and drainage. However, the therapeutic indications for multiple medium (5-10 cm) amoebic liver abscesses remain unclear. We herein report the findings of a 53-year-old woman who was receiving lenalidomide for multiple myeloma and subsequently developed multiple amoebic abscesses. Metronidazole alone was unsuccessful, although metronidazole and repeated percutaneous catheter drainage of the right lobe, left lobe, and thorax proved to ultimately be successful. Therefore, the successful use of medication alone may be associated with the total combined abscess volume.

Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection.

Cytomegalovirus polyradiculopathy in three Japanese patients with AIDS.

Polyradiculopathy (PRP) is a rare but serious neurologic complication of cytomegalovirus (CMV) in patients with acquired immunodeficiency syndrome (AIDS). We herein report three cases of CMV PRP in patients with AIDS. Although providing a prompt diagnosis and initiating anti-CMV therapy may achieve clinical improvements, administering single-drug treatment may result in virologic failure. Therefore, introducing antiretroviral therapy is a key step for improving the treatment outcomes of CMV PRP.

Clinically suspected acute myopericarditis with cardiac tamponade associated with peripheral blood eosinophilia presenting in early pregnancy: a case report.

INTRODUCTION: The clinical presentation of eosinophilic myocarditis may vary from asymptomatic to the manifestation of severe symptoms, including cardiac tamponade and arrhythmias. In pregnant patients with this condition, drugs must be used cautiously up to approximately the 4th month of pregnancy because drug use should be limited during the period of fetal organogenesis. CASE PRESENTATION: A 30-year-old Asian woman at 14 weeks of pregnancy with progressive malaise was hospitalized. The electrocardiogram revealed ST elevation and low QRS voltage. Echocardiography revealed massive pericardial effusion and myocardial swelling. A laboratory examination revealed an increase in her white blood cell count, with a predominance of neutrophils. Pericardial drainage was performed for relief of the cardiac tamponade. The pericardial effusion revealed an abundance of eosinophils. Subsequently, the peripheral blood eosinophil count began to rise, and the patient was clinically diagnosed with eosinophilic myopericarditis. The patient's condition improved rapidly following the initiation of prednisolone treatment, and she finally delivered a full-term normal infant. CONCLUSIONS: A patient with clinically suspected myopericarditis in the early stage of pregnancy who improved rapidly with pericardial drainage and prednisolone therapy, and successfully delivered a normal full-term infant; the diagnosis was made in the early stage of the disease, based on the detection of an abundance of eosinophils in the pericardial effusion preceding the subsequent development of peripheral blood eosinophilia.

A case of hereditary angioedema involving recurrent abdominal attacks.

A 44-year-old Japanese woman was diagnosed with type 1 hereditary angioedema (HAE) at the age of 30. In March 2007, she began suffering from severe abdominal pain due to intestinal edema. After treatment with C1-INH concentrate, her symptoms disappeared. However, during the subsequent three years, the frequency of the attacks increased continuously, and C1-INH concentrate was necessary for treatment of every attack. The increase in the number of attacks might have been due to the frequent injection of C1-INH concentrate or the deterioration of her disease course. In a genetic investigation, the patient was found to have a novel mutation in the C1-INH gene.