Hyperferritinemia: causes and significance in a general hospital.

OBJECTIVE: To elucidate conditions which cause elevation of the serum ferritin, extent of the elevation in each condition, and clinical relevance of hyperferritinemia in general practice. METHODS: We retrospectively studied medical records of all patients who had at least one serum ferritin measurement above 500 µg L-1. Patients who had a marked elevation of the serum ferritin over 10,000 µg L-1 were studied separately. RESULTS: We studied 1394 patients to identify the etiologies of hyperferritinemia. Median serum ferritin level was 1024 µg L-1 and 49.2% had ferritin levels of 501-1000 µg L-1. The most frequent cause of hyperferritinemia was non-human immunodeficiency virus infection followed by solid tumor, liver dysfunction, renal failure, and hematological malignancy. The distributions of the causes were different among groups stratified by the ferritin level. Forty-one percent had multiple causes and there was a tendency that the more underlying causes a patient had, the higher the ferritin level. Each condition led to a wide range of the ferritin level, and some patients could present with marked hyperferritinemia. Seventy percent of 111 patients with marked hyperferritinemia had multiple etiologies and a variety of diseases could lead to marked hyperferritinemia by themselves. DISCUSSION: Patients with hyperferritinemia frequently had multiple conditions. The level of the serum ferritin was determined by the underlying conditions to a certain extent; however, the variation was significant. While patients with marked hyperferritinemia mostly had multiple underlying causes, various diseases could cause hyperferritinemia by themselves. CONCLUSION: Hyperferritinemia is associated with both etiology and the number of underlying causes.

Simultaneous Presentation of Giant Cell Arteritis and Myelodysplastic Syndrome in an Elderly Japanese Man.

An 81-year-old Japanese man presented with constitutional symptoms and anemia and was diagnosed with giant cell arteritis (GCA) and myelodysplastic syndrome (MDS) simultaneously. His symptoms and anemia improved promptly with steroids; however, the MDS rapidly progressed to overt leukemia. While MDS patients are at an increased risk of autoimmune diseases, an association with GCA has rarely been reported. This case illustrates the importance of considering GCA as a cause of anemia in elderly patients if MDS is already diagnosed, even in countries where the prevalence of GCA is very low. The simultaneous development of GCA and MDS suggests a common pathogenetic link between these two diseases.

The Relationship Between Mean Platelet Volume and Fasting Plasma Glucose and HbA1c Levels in a Large Cohort of Unselected Health Check-Up Participants.

BACKGROUND: Larger platelets are more active and mean platelet volume (MPV) is an indicator of platelet activation and an independent risk factor of cardiovascular diseases. While MPV is reported to be higher in diabetic patients, the relationship between MPV and glycemic parameters in general population remains inconclusive. METHODS: In this cross-sectional study, we studied relationship between MPV and fasting plasma glucose (FPG) and HbA1c levels in 38,204 unselected participants of general health check-up aged 20 years or older in the year of 2014 who were considered to be representative of the general population. Individuals with known diabetes, coronary artery disease and/or cerebrovascular disease who were on drug therapy and those with platelet counts below 100 × 109/L or above 400 × 109/L were excluded. RESULTS: The mean age of the individuals was 52.3 ± 12.1 years and 46.1% were male. There were positive associations between MPV and both FPG (r = 0.066; P < 0.001) and HbA1c (r = 0.025; P < 0.001) levels when all individuals were analyzed as a whole. While the association was only marginal in individuals with HbA1c levels below 6.5% (r = 0.009; P = 0.068), it was significant in those with HbA1c ≥ 6.5% (r = 0.138; P < 0.001). When the individuals were categorized into four groups according to the HbA1c values: HbA1c < 5.5%, 5.5% ≤ HbA1c < 6.0%, 6.0% ≤ HbA1c < 6.5%, and HbA1c ≥ 6.5%, the mean MPV was virtually same among groups with HbA1c level < 6.5% and that of the individuals with HbA1c ≥ 6.5 was significantly higher than groups with lower HbA1c levels. Multivariate analyses adjusted with age and sex showed the same results. CONCLUSION: FPG and HbA1c appeared to be associated with MPV in unselected health check-up participants; however, the association between glycemic state and MPV was apparent only in individuals with impaired glycemic control and only marginal in those with normal glycemic control. The clinical significance of the associations warrants further study.

Iron Deficiency Anemia Due to the Long-term Use of a Proton Pump Inhibitor.

A 52-year-old man who had been taking omeprazole, a proton pump inhibitor (PPI), for 25 years developed iron deficiency anemia. An evaluation of the entire gastrointestinal tract did not reveal any possible causes of gastrointestinal blood loss. The cause of the iron deficiency was considered to be a reduction in gastrointestinal iron absorption in association with the reduced secretion of gastric acid due to PPI use. This case demonstrates that long-term PPI use for as long as 25 years may cause iron deficiency anemia and should be considered in the differential diagnosis of iron deficiency anemia in long-term PPI users.

The Experience of Persons With Hematological Malignancy When Communicating With Health Care Professionals.

This study aimed to elucidate the experiences of Japanese persons with hematological malignancy (PHMs) in communicating with health care professionals (HCPs), from diagnosis to the end of life, as recalled by their families. We interviewed 14 bereaved families and analyzed the data using the basic techniques of grounded theory. We found that PHMs lived to the fullest possible when they experienced ownership of their illness process despite their disease. The ownership was made possible by active communication from HCPs: first, acknowledging the PHM's way of life, including reaching out from the HCPs and appreciating sincerely PHMs' hopes and will; and second, paving the way ahead, including giving prospects and offering choices. The study underlines that rather than just providing information about the disease, HCPs need to actively ask about and show respect for the PHM's way of life. Only after achieving this can HCPs communicate possible future pathways with PHMs.

Overlap of IgG4-related Disease and Multicentric Castleman's Disease in a Patient with Skin Lesions.

A 59-year-old man presented with multiple dark red erythemas with induration, anemia, and polyclonal hypergammaglobulinemia. A skin biopsy revealed the infiltration of lymphocytes and plasma cells and he was initially diagnosed with multicentric Castleman's disease (MCD). Glucocorticoid treatment was only partially effective. Four years later, the patient's bilateral lacrimal glands gradually became enlarged and a biopsy revealed dense lymphocyte and plasma cell infiltration with an IgG4+/IgG+ plasma cell ratio of 70%. The patient was diagnosed with IgG4-related disease (RD). Rituximab only had a slight effect. This case demonstrates that overlapping features of IgG4-RD and MCD may present in a single patient, which suggests a shared pathogenesis.

Myelodysplastic Syndrome Developing Presacral Extramedullary Hematopoiesis with Atypical MRI Findings.

A 64-year-old woman was diagnosed to have refractory cytopenia with multilineage dysplasia (RCMD) including an increased number of sideroblasts in the bone marrow (BM). Computed tomography (CT) revealed a presacral mass which showed iso- or high-intensity signals according to T1-weighted and hypo-intensity signals on T2-weighted magnetic resonance imaging (MRI). CT-guided biopsy revealed the presence of hematopoietic tissue with features that correlated with the BM findings. While the formation of extramedullary hematopoiesis in the presacral area is rare, it is important to differentiate it from other parasacral tumors even though such differentiation is often difficult. This patient demonstrated atypical MRI signals possibly due to an increase in the cellular iron content of the erythroid precursors.

Hypertrophic Herpes Simplex Virus Type 1 Infection in a Patient With Acute Myeloid Leukemia.

A 64-year-old woman had a transformation from polycythemia vera to acute myeloid leukemia. While she was treated with azacitidine and prednisolone, a nodule at the left angle of the mouth developed, which was biopsied and diagnosed with hypertrophic herpes simplex virus type 1 (HSV-1) infection. The nodule resolved completely with aciclovir. While HSV type 2 virus occasionally forms mass or tumoral lesions in immunocompromised, especially acquired immunodeficiency syndrome, patients, it is extremely rare that HSV-1 infection leads to similar lesions. The hematological conditions and the therapies given may have contributed to the rare manifestation of HSV-1 infection.

Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies.

While cigarette smoking is a well-recognized cause of elevated white blood cell (WBC) count, studies on longitudinal effect of smoking cessation on WBC count are limited. We attempted to determine causal relationships between smoking and elevated WBC count by retrospective cross-sectional study consisting of 37,972 healthy Japanese adults who had a health check-up between April 1, 2008 and March 31, 2009 and longitudinal study involving 1730 current smokers who had more than four consecutive annual health check-ups between April 1, 2007 and March 31, 2012. In the cross-sectional study, younger age, male gender, increased body mass index, no alcohol habit, current smoking, and elevated C-reactive protein level were associated with elevated WBC count. Among these factors, current smoking had the most significant association with elevated WBC count. In subgroup analyses by WBC differentials, smoking was significantly associated with elevated counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Ex-smoking was not associated with elevated WBC count. In the longitudinal study, both WBC and neutrophil counts decreased significantly in one year after smoking cessation and remained down-regulated for longer than next two years. There was no significant change in either WBC or neutrophil count in those who continued smoking. These findings clearly demonstrated that current smoking is strongly associated with elevated WBC count and smoking cessation leads to recovery of WBC count in one year, which is maintained for longer than subsequent two years. Thus, current smoking is a significant and reversible cause of elevated WBC count in healthy adults.

A Newly Characterized Hemoglobin Variant with a High Oxygen Affinity, Hb Fuchu-II, Presenting with Acute Myocardial Infarction.

A 65-year-old Japanese man presented with acute myocardial infarction (AMI) and polycythemia. Biochemical studies of the patient's hemoglobin (Hb) and the sequencing of his globin genes revealed that the polycythemia was secondary to a high oxygen affinity Hb variant, Hb Fuchu-II. Hb variants with high oxygen affinity can be an additional thrombotic risk factor in older patients and/or those with other risk factors. The patient was diagnosed with hemoglobinopathy after the development of AMI and exemplifies the importance of recognizing such conditions and of taking appropriate prophylactic interventions.

Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease.

A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected.

Pulmonary Extranodal Marginal Zone Lymphoma with Macroglobulinemia and Mixed Cryoglobulinemia Developed in a Patient with Chronic Hepatitis C.

We report a 65-year-old woman with a chronic hepatitis C virus infection who developed pulmonary extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissues complicated with macroglobulinemia and mixed cryoglobulinemia. She was treated with immunochemotherapy which resulted in the reduction of both the tumors and the serum immunoglobulin (Ig) M level. This case exemplifies an extensive stimulation upon immune system with derangement in the production of immunoglobulines associated with EMZL, and suggests that it is necessary to consider the possibility of B-cell lymphoma when IgM paraprotein is detected.

Relapse of immune thrombocytopenia associated with varicella 20 years after splenectomy.

A 45-year-old man who had undergone splenectomy 20 years earlier for immune thrombocytopenia (ITP) presented with a fever, arthralgia and vesicular skin rash. The skin rash was typical for varicella, as confirmed on serological studies. He exhibited isolated thrombocytopenia and was diagnosed with ITP. In addition, an accessory spleen was detected. The platelet count responded to treatment with prednisolone (PSL), and the varicella subsided uneventfully following therapy with acyclovir. Furthermore, the platelet count was maintained after PSL was discontinued. This case suggests an etiological link between varicella and very late relapse of ITP after initial splenectomy.

Primary Sjögren syndrome presenting with hemolytic anemia and pure red cell aplasia following delivery due to Coombs-negative autoimmune hemolytic anemia and hemophagocytosis.

A 36-year-old woman presented with hemolytic anemia without a reticulocyte response 38 days after delivery. A marked reduction in erythroid cells and an increase in macrophages with active hemophagocytosis were noted in the bone marrow. While conventional Coombs' tests were negative, the level of red blood cell (RBC)-bound immunoglobulin G (IgG) was increased. The patient was diagnosed with primary Sjögren syndrome (pSS) based on her symptoms, positive anti-SS-A antibodies, Coombs-negative autoimmune hemolytic anemia and pure red cell aplasia associated with RBC-bound IgG and hemophagocytosis. The unique presentation was considered to be a consequence of immunological derangement associated with pSS, pregnancy and delivery.

Ischemic heart disease due to compression of the coronary arteries by malignant lymphoma.

A 76-year-old man presented with a two-month history of angina pectoris. Computed tomography (CT) revealed a serial enlargement of the supraclavicular and mediastinal lymph nodes compressing the heart, pulmonary artery and aorta. CT angiography (CTA) showed stenosis of the coronary arteries as a result of compression by the enlarged lymph nodes. First-pass contrast-enhanced cardiac magnetic resonance imaging (MRI) at rest revealed a perfusion defect, thus indicating myocardial ischemia. Diffuse large B-cell lymphoma was diagnosed and multidrug combination chemotherapy led to prompt improvement of the symptoms. Relief of the stenosis in the coronary arteries and improvements in myocardial perfusion were noted on follow-up CTA and MRI.

Professionalism Mini-Evaluation Exercise for medical residents in Japan: a pilot study.

CONTEXT: Assessing medical professionalism among medical residents is of great importance. The Professionalism Mini-Evaluation Exercise (P-MEX) is a tool for assessing professionalism that was developed, tested for reliability and validated in Canada. Prior to the present study, no Japanese version of the P-MEX had been tested. METHODS: We modified the P-MEX for use in Japan and tested it on medical residents in a Japanese teaching hospital. For each resident, eight evaluators completed the P-MEX forms. A total of 184 P-MEX forms were completed on 23 senior residents. The construct validity of the P-MEX was analysed by confirmatory factor analysis through structural equation modelling. The reliability of the P-MEX was tested using generalisability theory and a decision study. After performing the assessment and providing feedback to the residents, we conducted a survey on the residents' perceptions of the assessment. RESULTS: Results indicate content and construct validity. A confirmatory factor analysis revealed that factor loadings ranged from 0.58 to 0.96, indicating good construct validity except for one item (P12: Maintained appropriate boundaries with patients and colleagues). Structural equation modelling showed that adding new items developed in Japan to the P-MEX provided adequate factor validity. A decision study showed confidence intervals sufficiently narrow with as few as 10 evaluations, slightly more than the eight forms verified in Canada. Most residents stated that the items were reasonable and appropriate, the results of the assessment were consistent with their own self-evaluation and the assessment enhanced their motivation. CONCLUSIONS: Our study demonstrated good evidence of adequate reliability and validity of the P-MEX for the assessment of professionalism among Japanese residents. Moreover, the addition of new items developed in Japan provided adequate factor validity.