An immunocompromised patient presented with febrile episodes, an erysipelas-like rash, and thromboembolic complications. Amplification of 16S rRNA gene sequences from blood and sequence analysis revealed "Candidatus Neoehrlichia mikurensis." We report the first case of human disease caused by "Ca. Neoehrlichia mikurensis." CASE REPORTA 77-year-old man with B-cell chronic lymphocytic leukemia developed autoimmune anemia in 2007 and started long-term treatment with corticosteroids. In September of the same year, he had a transitory ischemic attack. Since his hemolytic anemia worsened despite treatment with corticosteroids, he was given courses of cyclophosphamide during the second half of 2008. The patient developed autoimmune thrombocytopenia (platelet count, 38 ϫ 10 9 /liter; reference range for healthy adults, 145 ϫ 10 9 to 355 ϫ 10 9 /liter) and was splenectomized laparoscopically on 4 June 2009, with subsequent normalization of platelet counts.While kayaking on 3 July 2009, the patient developed acute diarrhea, which was followed by fever and chills and a short episode of loss of consciousness the same night. When admitted to Kungälv Hospital, Kungälv, Sweden, the next day under suspicion of sepsis, he was hypotensive (blood pressure [BP], 85/60 mm Hg) and febrile (temperature, 38.5°C; reference, Ͻ38.0°C). Deep vein thrombosis in the left lower extremity encompassing the groin and pulmonary embolism were also discovered. The patient was treated intravenously (i.v.) with ceftazidime for 1 week, but no microbe was identified. The patient's systemic inflammatory reaction (C-reactive protein level of 92 mg/liter [reference, Ͻ5 mg/liter] and fever) was judged to result from widespread thromboembolism, and the patient was discharged on 10 July with low-molecular-weight heparin medication.A month later, the patient was readmitted to Sahlgrenska University hospital with a fever of 39.5°C, BP of 105/55 mm Hg, and an erysipelas-like rash on the inside of the left leg. The patient was anemic (hemoglobin [Hb], 85 g/liter; reference range, 134 to 170 g/liter) and had leukocytosis (white blood cell [WBC] count, 11 ϫ 10 9 /liter; reference range, 3.5 ϫ 10 9 to 8.8 ϫ 10 9 /liter) with a pronounced left shift, a normal platelet count, and a C-reactive protein level of 54 mg/liter (reference, Ͻ5 mg/liter). Hyponatremia was present (sodium level, 134 mmol/liter; reference range, 137 to 145 mmol/liter). The patient was taking warfarin, oral prednisolone, omeprazole, and vitamin B tablets. He was treated with i.v. cloxacillin for 2 days, followed by oral floxacillin (flucloxacillin) for 2 days and, finally, i.v. meropenem for 7 days (Fig. 1). Fever, elevated levels of C-reactive protein, and hyponatremia resolved within 1 week, apparently after the institution of meropenem (Fig. 1). All cultures (three blood cultures, two urinary cultures, and one oral swab culture) were negative. A chest X ray revealed scant infiltrates around the hili and in the basal part of the right lung, but computed tomography (CT) scans of the thorax and ...

Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70–80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000–2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06–2.64) cases per million inhabitants per year. Median age was 60 years (range: 2–92), and median follow up was 76 (0–193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0–18 years, 90.5% in patients aged 19–39 years, 70.7% in patients aged 40–59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40–59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

Not available.

Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.

While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids.

Background and aims. Aplastic anemia (AA) is a rare but life-threatening disease. The introduction of immunosuppressive treatment (IST) and hematopoietic stem cell transplantation (HSCT) has considerably improved the outcome of patients with AA. However, modern-day population-based data are limited. This thesis aimed to retrospectively analyze the incidence, treatment modalities, survival, and immune markers in the bone marrow of patients diagnosed with AA in Sweden from 2000-2011. Patients and methods. Patients were included via the National Patient Registry and diagnosed according to the Camitta criteria. All data were collected from medical charts. In paper IV, immunohistochemistry was used to obtain data on regulatory T cells and macrophages in the bone marrow. Results and conclusions. We identified 257 confirmed cases, with an overall incidence of 2.35 cases per million inhabitants per year. The 5-year overall survival (OS) was >90% in patients aged up to 39 years but 38.1% in patients aged ≥60 years. Multivariate analysis showed that age ≥40 years, very severe AA, and no specific therapy were independent risk factors for inferior survival. First-line IST treated patients (n=158) showed a 47% response rate with no difference regarding the age groups or anti-thymocyte globulin (ATG) formulation. The response was significantly associated with the severity grade at the time of treatment initiation, and very severe AA patients exhibited a response rate of 22%. Sixty-eight patients underwent HSCT with a 5-year OS of 86.8%. The graft-versus-host-disease-free, relapse/rejection-free survival at 5 years was 69.1%. Patients aged ³40 years had higher transplant-related mortality that translated into a lower 5-year OS. In paper IV, we found lower numbers of FOXP3-positive regulatory T cells in AA patients without predictive value for IST response and that patients with a higher number of CD163-positive macrophages had a better 5-year OS, but this benefit was only observed in the non-severe AA group. In conclusion, younger patients have very good long-term survival regardless of the choice of therapy, whereas the outcome for patients ≥60 years remains poor. Very severe AA patients respond poorly to ATG, which indicates the need for a different treatment approach.

No abstract