Imported human rabies in Switzerland, 2012: a diagnostic conundrum.

Human rabies is rare in Western Europe. It is not easily recognized in the absence of a history of exposure. We describe the clinical course, diagnosis and follow-up of an imported human rabies case in Switzerland. The patient, a U.S. citizen, presented at an outpatient clinic in Iraq with pain in his right shoulder on July 5, 2012. On July 8 he was transferred to a hospital in the United Arab Emirates, where he exhibited progressive encephalitis with coma. On July 29, he was transferred to a hospital in Switzerland, where he died on July 31, 2012. The autopsy showed severe encephalitis. Rabies was diagnosed by the rapid fluorescent focus inhibition test (RFFIT) and confirmed by fluorescence antibody testing (FAT) in brain smears and immunohistochemistry on paraffin-embedded brain sections. The viral strain was characterized by RT-PCR followed by sequencing and phylogenetic analysis as an American bat rabies strain associated with Tadarida brasiliensis. Close contacts and exposed health care workers received postexposure prophylaxis (PEP).

Rhinofacial Conidiobolus coronatus infection presenting with nasal enlargement.

Rhinofacial Conidiobolus coronatus infection is a rare form of zygomycosis in humans living in the northern hemispheres. Most human cases are observed in the periequatorial areas of Africa, Asia, or South America. Only limited information regarding optimal treatment is available. We report a case of rhinofacial C. coronatus infection in an emigrated Sudanese patient. The infection was successfully treated with terbinafin and itraconazole for 12 months. Diagnosis was confirmed by microbiological culture from a tissue biopsy. Antimicrobial susceptibility testing of this organism was not predictive of optimal therapy.

Venous thromboembolism prophylaxis in acutely ill medical patients: definite need for improvement.

AIM OF THE STUDY: To examine the frequency and adequacy of thromboprophylaxis in acutely ill medical patients hospitalized in eight Swiss medical hospitals. METHODS: A cross-sectional study of 1372 patients from eight Swiss hospitals was carried out. After exclusion of patients (275) given therapeutic anticoagulation, 1097 patients were audited. The adequacy of thromboprophylaxis was assessed by comparison with predefined explicit criteria. RESULTS: Of 1097 patients, 542 (49.4%) received thromboprophylaxis. According to the explicit criteria, 644 (58.7%) should have been on prophylaxis (P < 0.001, when compared with the rate observed). The rate of prevention differed widely between hospitals (from 29.4 to 88.6%) with no difference between teaching and nonteaching hospitals. According to the explicit criteria, a substantial proportion (44.9%) of the patients who should have been treated were not. Conversely, 41.3% of the patients were unnecessarily treated. CONCLUSIONS: Even though the appropriateness of the explicit criteria used could be challenged, our data suggest that the current practice is associated with important uncertainty leading to both overuse and underuse of thromboprophylaxis in patients hospitalized in medical wards. More efforts are urgently needed to develop new or endorse existing explicit, evidence-based criteria and guidelines for thromboprophylaxis in this population of patients.

Prolonged course of pure red cell aplasia after erythropoietin therapy.

Pure red cell aplasia (PRCA) caused by neutralising anti-erythropoietin antibodies is a very rare disease. Since 1998, an increased incidence of PRCA in patients with kidney failure following treatment with recombinant human erythropoietin (rhEpo) has been reported, mostly in Europe. In most cases, PRCA was cured by immunosuppressive therapy, immunoglobulins, plasmapheresis or renal transplantation. We report an exceptionally prolonged course of PRCA over 68 months despite renal transplantation and different immunosuppressive regimens.

Factor Xa and thrombin, but not factor VIIa, elicit specific cellular responses in dermal fibroblasts.

UNLABELLED: Coagulation factors (F)VIIa, FXa and thrombin are implicated in cellular responses in vascular, mesenchymal and inflammatory cells. Fibroblasts are the most abundant cells in connective tissue, and damage to blood vessels places coagulation factors in contact with these and other cell types. OBJECTIVES: To investigate cellular responses of primary dermal fibroblasts to FVIIa, FXa and thrombin by following changes in expression of candidate proteins: monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and to determine the expression of receptors implicated in signaling by these coagulation factors. METHODS: Steady-state mRNA levels were quantified by RNase protection assay, and protein secretion by ELISA. PAR gene expression was assessed by ribonuclease protection assay and conventional and quantitative reverse-transcription-polymerase chain reaction. RESULTS: FVIIa did not induce the candidate genes. In contrast, FXa and thrombin induced MCP-1 mRNA and protein secretion strongly, IL-8 moderately, and IL-6 weakly. Neither FXa nor thrombin induced VEGF mRNA or protein secretion, although FXa induced VEGF protein secretion in lung fibroblasts. Comparison of the presence of candidate receptors in the two fibroblast subtypes demonstrated higher levels of PAR-1 and PAR-3 in lung fibroblasts relative to their dermal counterparts and the additional expression of PAR-2. CONCLUSIONS: FXa and thrombin induce expression of MCP-1, IL-8 and IL-6, and distribution and expression of PARs on dermal fibroblasts is reduced relative to their lung counterparts. Tissue origin may influence the cellular response of fibroblasts to coagulation proteases.

Successful reintroduction of methotrexate after acute pneumonitis in a patient with acute lymphoblastic leukemia.

Low-dose methotrexate (MTX) is used as disease-modifying therapy in severe rheumatoid arthritis and as maintenance treatment in patients with complete remission of acute lymphoblastic leukemia (ALL). It is generally well tolerated, but in 27% of patients acute pneumonitis leads to discontinuation of treatment. We describe a 56-year-old female patient with newly diagnosed pre-B-ALL. She was treated with induction chemotherapy in July 1999 which lead to complete remission. Maintenance treatment with low-dose MTX and 6-mercaptopurine (6-MP) was started in December 1999. In April 2000 she was hospitalized because of fever, cough, and rapidly progressive dyspnea. No pathogens could be cultured from blood or bronchoalveolar lavage fluid. Computed tomography of the lungs revealed interstitial infiltration and ground-glass opacities. Acute pneumonitis was diagnosed, and MTX was stopped. Prednisone therapy lead to rapid clinical amelioration of dyspnea and hypoxemia. Since for this patient there was no alternative leukemia therapy, MTX was successfully reintroduced in August 2000 without reappearance of any respiratory symptoms. We discuss risk profile, clinical and histological presentation, and therapy of MTX-induced pneumonitis. To our knowledge, this is the first patient with ALL in whom successful reintroduction of MTX after severe pneumonitis has been reported.

Pulmonary granulomas after tumour necrosis factor alpha antagonist therapy.

Tumour necrosis factor alpha (TNFalpha) antagonists are an established therapeutic option in Crohn's disease and rheumatoid arthritis. In recently published studies these agents have been used with great success, but little is known about any side effects or long term consequences. They increase the frequency of infections with mycobacteria, where TNFalpha is thought to be an important host defence factor. We describe one patient who was treated with TNFalpha antagonists and later developed pulmonary granulomas with caseating necrosis without detection of mycobacteria or any other pathogens. Possible mechanisms involved in this newly recognised side effect are discussed.

Life-threatening thrombocytopenia associated with acute Epstein-Barr virus infection in an older adult.

Acute Epstein-Barr virus (EBV) infection commonly induces hematological abnormalities, most notably atypical lymphocytosis ("infectious mononucleosis"). In addition, mild decreases in platelet counts are commonly encountered in uncomplicated cases; however, severe thrombocytopenia is exceedingly rare. Here, we describe a 58-year-old white man who presented with cervical lymphadenopathy, thrombocytopenia, and a bleeding diathesis with minimal platelet counts of 0.5 x 10(9)/l. The diagnosis of acute EBV was serologically confirmed. Because of the bleeding diathesis and the prior ingestion of aspirin, treatment was started with intravenous methylprednisolone and immunoglobulins. Platelet counts normalized within 7 days, and the patient fully recovered. Although more common in children, adolescents, and young adults, acute EBV infection may also occur in older adults, and this differential diagnosis should be considered in every patient presenting with acute thrombocytopenia. In this report we also briefly summarize the literature on EBV-associated severe thrombocytopenia.