Volume 31, Issue 5

The diagnosis and localisation of cerebrospinal fluid (CSF) fistulae of spontaneous or traumatic origin remain a challenge in clinical practice, involving various medical specialties (orthopaedic surgery, ear, nose and throat, neurosurgery, oral surgery). Detection of CSF-specific proteins is recommended to confirm the diagnosis. β-2 Transferrin and β-trace protein (prostaglandin D synthase) are established qualitative and quantitative assays to detect such a fistula. Surgical closure of the CSF fistula requires proper localisation using radiological methods in combination with intrathecally applied tracer compounds.

Zusammenfassung Den wichtigsten Stellenwert für die In-vitro-Diagnostik von Nahrungsmittelallergien hat die Bestimmung des allergenspezifischen Immunglobulin E (IgE), i. d. R. nach Anamnese und Hauttest durchgeführt. Hunderte von Einzelallergenen und Kombinationen werden von einer Reihe von Herstellern angeboten. Unterschiedliche Allergene, Detektions- und Kalibrierungsmethoden erlauben selten einen direkten Vergleich der Resultate; sie können außerdem erheblich von den anamnestischen Angaben, den Ergebnissen im Hauttest und in der oralen Provokation abweichen. Zelluläre Laborverfahren (Histamin-Release-, Basophilen-Aktivierungs-Test und Leukotrien-freisetzungstest/CAST) sind für die Diagnostik von IgE-vermittelten Nahrungsmittelallergien derzeit nur in Einzelfällen bzw. für wissenschaftliche Fragestellungen zu empfehlen. Nahrungmittelallergene: Klassische Nahrungsmittelallergene (häufiger im Kindesalter) bereiten als stabile Proteine selten Schwierigkeiten für die IgE-Diagnostik. Eine Bestimmung des IgE gegen definierte Proteine (z. B. Einzelallergene aus Kuhmilch oder Hühnerei) statt gegen das Gesamtprotein bringt gegenwärtig keine Vorteile für die Routinediagnostik. Bei Pollen- oder Latexsensibilisierung wird häufig IgE gegen kreuzreaktive, vorwiegend instabile Allergene in diversen Obst-, Gemüse- und Pflanzensorten nachgewiesen, das nur bei korrespondierenden Symptomen klinisch relevant ist – ein weiteres Argument für eine verdachtsorientierte, gezielte In-vitro-Diagnostik. Indikationen für die IgE-Dianostik: begründeter Verdacht einer Nahrungsmittelallergie, aber keine klare Aussage nach Anamnese und Hauttest, Sensibilisierung auf Hauttest-ungeeignete Nahrungsmittel, bedrohliche Reaktion auf Nahrungsmittel, Hauttest bzw. seine Auswertung nicht möglich. Interpretation der Ergebnisse: falsche Ergebnisse durch unzureichende Reagenzienqualität oder Laborfehler (technische und methodische Fehler), klinisch nicht relevante Ergebnisse durch stark erhöhtes Gesamt-IgE, zu hohe Nachweisempfindlichkeit oder kreuzreagierende Allergene (Interpretationsfehler). Untauglich zur Nahrungsmittelallergie-Diagnostik: spezifisches IgG, zytotoxischer Lebensmitteltest, Elektroakupunktur, Bioresonanz (Methoden ohne Aussagekraft und/ oder Überprüfung). Ungelöste Probleme: optimale Qualität der Reagenzien, Kalibration und Vergleichbarkeit unterschiedlicher Methoden, serologische Kreuzreaktivität. Zukünftige Studien zur klinischen Relevanz der In-vitro-Ergebnisse werden die Diagnostik und Beurteilung einer Nahrungsmittelallergie verbessern helfen. Abstract Measurement of allergen-specific immunoglobulin E (IgE) represents the most useful diagnostic in vitro test in food allergy and is usually performed after a case history and skin test. Hundreds of single allergens and combinations are offered by a number of manufacturers. Different allergens, detection and calibration methods lead to a lack of comparability of test results, which can also differ substantially from case history, skin test and food challenge results. Cellular laboratory tests (histamine release, basophil activation test, leukotriene production/cellular antigen stimulation test) should be used for food allergy testing only in individual cases or controlled studies. Food proteins of higher stability (predominantly occurring in early infancy) rarely cause problems in terms of IgE testing. At present, the use of defined proteins (i.e., single allergens from cow's milk or hens eggs) for routine diagnosis of allergen-specific IgE has no advantage compared to whole food allergens. Resulting from sensitization to pollen allergens or latex, IgE will be found to be cross-reactive, mostly to labile allergens from various fruit, vegetable and plant species, which is clinically relevant only in the case of corresponding symptoms. This supports the recommendation of selected in vitro testing, focussing on suspected foods. Indications for IgE testing include a resonable probability of food allergy, but no clear-cut evidence after case history and skin test, sensitization to foods not suitable for skin testing, severe reactions to foods, or when a skin test or its interpretation is not possible. False positive or negative results can be due to inappropriate reagents or laboratory errors (technical or methodological pitfalls), while clinically irrelevant results may be due to strongly elevated total serum IgE, low cutoff levels or cross-reactive allergens (errors due to false interpretation). Allergen-specific IgG, cytotoxic food tests, electroacupuncture, and bioresonance are not suitable for diagnosis as these are methods without any value and/or missing evidence. Unsolved problems include optimized reagent quality, the calibration and comparability of results from different methods, and serological crossreactivity. Future studies addressing the clinical relevance of in vitro results will help to improve the diagnosis and interpretation of food allergy.

Hymenoptera venom-allergic patients with mast cell disease, i.e., mastocytosis and/or elevated basal serum tryptase concentration, are at high risk of severe, life- threatening sting reactions. Specific immunotherapy with honey bee or vespid venom is urgently indicated for these patients. Basically, efficacy of immunotherapy is not reduced in these patients. However, it is frequent that a higher maintenance dose than the standard dose of 100 μg is needed. For this reason, a sting challenge test to assess treatment efficacy is particularly important. Immunotherapy with honey bee venom, which is less effective than treatment with vespid venom, is performed with an increased maintenance dose of 200 μg from the start. Also, in patients with mast cell disease life-long continuation of specific immunotherapy is indicated. To identify mast cell disease, careful inspection of the skin for cutaneous mastocytosis as well as measurement of basal serum tryptase concentration is necessary. If mast cell disease is identified, further assessment has to be carried out so as not to overlook systemic mastocytosis.

The future “Guideline of the Federal Medical Association for quality assurance in laboratory medicine” will lead to the mandatory implementation of elements of a comprehensive quality management system in medical laboratories. In contrast, in both areas subject to statutory legislation and private areas, accreditation of medical laboratories according to EN ISO 15189 and EN ISO/IEC 17025 is still performed voluntarily. On the basis of the German Medical Device Act, the future guideline provides quality requirements for all medical practitioners that go far beyond the quality assurance measures in the analytical phase of medical laboratory analysis. The basic requirements of EN ISO 15189 referring to personnel, premises, environmental conditions, equipment, the pre-analytical phase and the quality management system are considered in the new guideline. However, the guideline is of statical character and describes an extended quality assurance system rather than a process-oriented quality management system in terms of international quality management principles. The German accreditation system will be considerably influenced by both the new Guideline of the Federal Medical Association and future European regulations concerning accreditation.

With the increasing availability of automatic analysers that can process a large number of specimens in a short time, the manufacturers of diagnostic instruments have opened the door to industrial mass production in the clinical laboratory. Work that was previously performed manually has been transferred to automatic analysers, thereby increasing productivity and decreasing costs. The economic pressure of recent years has initiated a process in Europe that started 20–30 years ago in Japan and the US. Technical improvements, particularly in information technology (IT), have led to the automation of pre-analytical steps in addition to the analytical step. Such systems automatically scan, centrifuge, decap, and archive samples. These so-called total laboratory automation (TLA) systems commonly use a conveyer belt to transport samples to the analytical modules. At present, all clinical laboratories need to consider the introduction of laboratory automation to reduce staff costs, which amount to up to 70% of the total laboratory budget. To decide on an appropriate system, it is mandatory to carefully analyse the workload and workflow. In addition, the pros and cons of different vendors should be balanced. An important point to consider is the IT control of the TLA system and its integration into the IT concept of the laboratory. Favourable and intelligent laboratory automation leads to improvements in patient care and releases laboratory staff from activities with low added value. Profitable laboratory service cannot be achieved in large hospital laboratories in the future without laboratory automation. Selection of a suitable automation solution can make the laboratory a valuable partner in decreasing costs of a hospital.

Efficiency is of utmost importance in public healthcare under constantly increasing cost pressure. An important determinant of efficiency in the public health sector is laboratory diagnostics. In the absence of reliable and rapidly available laboratory results, treatments are delayed and operations are postponed. One solution to help overcome these challenges is workflow management with order entry. Two years ago, a pilot project on order entry was initiated at the University of Göttingen Medical Centre. Small, flexible barcode printers were installed in the ward offices and order entry screens were established on the PCs. Using a few PC commands, analyses are marked on the screen. Simultaneously with online entry, barcode labels with all the necessary information are printed and seal-colour marked in accordance with the blood sampling tubes. Tubes equipped with the correctly coloured barcode are sent to the laboratory and are integrated into the laboratory system.