Das Hepatitis C-Virus und rheumatische Erkrankungen

Zusammenfassung Die Hepatitis C-Virus (HCV)-Infektion ist eine für die rheumatologische Praxis relevante Infektionserkrankung. Sie ist Ursache der gemischten Kryoglobulin?mie. Zus?tzlich entwickeln viele HCV-Patienten rheumatische Begleitmanifestationen. Rheumatologisch relevante Manifestationen sind: Sicca-Syndrom, thromboembolische Ereignisse bei Vorliegen von Anti-Kardiolipin-Antik?rpern und Fibromyalgiesyndrom. Ebenfalls HCV-assoziiert, ist eine zumeist seropositive polyartikul?re Arthritis. Diese erfüllt die klinischen Kriterien der chronischen Polyarthritis, nimmt aber einen anderen Verlauf. Remissionen werden h?ufig beobachtet, erosive Verl?ufe sind die Ausnahme. Folgende Autoantik?rper sind mit der HCV-Infektion assoziiert: Kryoglobuline, Rheumafaktoren, Anti-Nukle?re-Antik?rper (ANA), Antik?rper gegen glatte Muskulatur (SMA), Anti-Phospholipid-Antik?rper, Schilddrüsenautoantik?rper. Antik?rper gegen Ro und La sind bei der HCV-Infektion nicht nachweisbar. Da die Leberentzündung zumeist okkult verl?uft, ist auch bei normalen Lebertransaminasen eine HCV-Infektion nicht ausgeschlossen und die Indikation zur HCV-Testung gegeben, wenn bestimmte serologische und klinische Hinweise vorliegen. Bei positivem HCV-Nachweis sollte auf hepatotoxische Medikamente verzichtet und die M?glichkeit einer viruseradizierenden Therapie mit α-Inferferon erwogen werden. Eingegangen: 23 Dezember 1996 Akzeptiert: 15 September 1997     

Pulmonale Hypertonie

Zusammenfassung Die Aufschlüsselung der genetischen Ursachen der pulmonalen Hypertonie hat sich in den letzten Jahren zu einem dynamischen Forschungsgebiet in der Pneumologie entwickelt. So konnte gezeigt werden, dass die familiäre und z. T. auch die idiopathische Form der pulmonalarteriellen Hypertonie mit Veränderungen auf dem Chromosom 2q31–32 einhergeht. Die detaillierte Identifizierung des zugrunde liegende Genlocus, des BMPR2, hat entscheidende neue Impulse zum pathophysiologischen Verständnis dieser Erkrankung gegeben. Dieser Genlocus kodiert einen Transmembranrezeptor der TGF -Superfamilie, einer Familie von Wachstumsfaktoren, welche Schlüsselfaktoren für Proliferation und Differenzierung vieler Zelltypen darstellen. Im Folgenden fassen wir die für das Verständnis der pulmonalen Hypertonie relevanten genetischen und funktionell genomischen Forschungsergebnisse zusammen.     

Pulmonale Hypertonie

The first clinical classification and hemodynamic definition of pulmonary hypertension (PH) was introduced at a WHO meeting in Geneva in 1973. The diagnostic classification was updated at the world conference in Evian, 1998, introducing 5 clinical groups instead of the original groups of primary and secondary PH. Although changes have been made, the basic structure of this classification was adopted in the following world congresses in Venice 2003 and Dana Point 2008. Since 1973, PH was hemodynamically defined as mean pulmonary arterial pressure (PAP) >25 mmHg at rest or >30 mmHg during exercise. In 2008, the hemodynamic definition was discussed again. The analysis of the published data, based on invasive measurements in healthy individuals, suggested that resting PAP is 14.0±3.3 mmHg and independent of gender and is only mildly influenced by posture and age. During exercise, however, PAP is dependent on exercise level and age. Accordingly, the Dana Point statement defines the normal range of resting mean PAP between 8 and 20 mmHg and PH as resting mean PAP ≥25 mmHg. The exercise part of the old definition of PH was abandoned.     

Pulmonale Hypertonie

Pulmonary hypertension (PH) is a devastating disease that, if untreated, is characterized by a poor prognosis. According to the current classification (Venice, 2003), pulmonary arterial hypertension (PAH) is distinguished from other forms of PH. Recent advances in drug therapy have led to a dramatic improvement in medical care, particularly in patients with PAH. Hence, early establishment of the diagnosis and a precise classification appear increasingly important. This review provides an overview on the definition, classification, pathophysiology, and clinical presentation of various forms of PH. Furthermore, it summarizes the recommended diagnostic work-up and current treatment options, particularly for PAH, with special emphasis on prostanoids, endothelin receptor antagonists (ERAs), and phosphopdiesterase type 5 (PDE5) inhibitors such as sildenafil. Finally, novel developments are discussed which currently represent an exciting field of basic and clinical research.     

Pulmonale Hypertonie

Pulmonary hypertension has dramatically evolved as a new scientific field triggered by the development of targeted pulmonary arterial hypertension (PAH) therapies. Pulmonary hypertension is defined by elevated resting pulmonary arterial pressures but the definition of normal values during exercise is currently not possible. Diagnostic tools include the history, physical examination, electrocardiography (ECG), thoracic X-ray and echocardiography. In scleroderma patients a reduced diffusing capacity of the lungs for carbon monoxide (DLCO) is a marker of PAH. Approved PAH therapies include three prostanoids, two endothelin receptor antagonists and two phosphodiesterase 5 inhibitors. These therapies have substantially improved the prognosis of PAH patients. A novel soluble guanylate cyclase (sGC) stimulator has been submitted for approval. There are increasing numbers of elderly PAH patients who have an adverse prognosis as compared with classical PAH patients. In particular those with simple or combined heart and lung diseases pose a challenge for the future.     

Pulmonale Hypertonie und Rechtsherzversagen auf der Intensivstation

The management of pulmonary hypertension and right ventricular failure in hemodynamically unstable patients is one of the most challenging situations in critical care medicine. Inadequate therapy, e.g. aggressive fluid resuscitation or invasive ventilation, may even harm patients with pulmonary hypertension. Identifying the underlying etiology therefore remains the primary focus for initiating successful management of patients with decompensated pulmonary hypertension and right ventricular failure. Pulmonary embolism requires immediate restoration of pulmonary vascular patency. The body of evidence from studies is scarce and favors dobutamine, NO inhalation, and intravenous prostacyclin. However, the use of other vasoactive substances, inotropes, and supportive measures has been successful in individual patients; it should be guided by the expected effects on the pulmonary vasculature or right ventricle, and should be adapted to the patient’s concomitant diseases.     

Kapillarmikroskopie und rheumatische Erkrankungen: State of the art

Nailfold capillaroscopy (NVC) represents the best method for analyzing microvascular abnormalities in rheumatic diseases. Raynaud’s phenomenon (RP) represents the most frequent clinical aspect of microvascular involvement and is a key feature of several such diseases. Under normal conditions or in primary RP (exclusion by the cold-exposure test), the normal nailfold capillaroscopic pattern shows a regular disposition of the capillary loops within the nail bed. However, in subjects suffering from secondary RP, one or more alterations in the capillaroscopic findings should alert the physician to search for an underlying connective tissue disease. Architectural disorganization, giant capillaries, hemorrhages, loss of capillaries and avascular areas characterize more than 95% of patients with overt systemic sclerosis (sclerodema, SSc). Therefore, the term “scleroderma pattern”, includes all capillaroscopic changes typical of the microvascular involvement in SSc. The capillaroscopic aspects observed in dermatomyositis and in undifferentiated connective tissue disease are generally reported as “scleroderma-like patterns”. This peripheral microangiopathy can be effectively detected early in the course of the disease and studied in detail by nailfold capillaroscopy or, better, with NVC. In addition, early differential diagnosis between primary and secondary RP is the greatest advantage NVC has to offer. In addition, interesting capillaroscopic changes have been observed in systemic lupus erythematosus, antiphospholipid syndrome and Sjögren’s syndrome. However, further epidemiological and clinical studies are needed to better standardize NVC patterns.     

Pulmonale Hypertonie nach Lungenarterienembolie

Ohne Zusammenfassung     

Pulmonale Hypertonie bei Lungenerkrankungen

Pulmonary hypertension is frequently associated with chronic lung diseases. There is ample evidence linking lung disease plus pulmonary hypertension with an adverse prognosis. However, data demonstrating a positive effect of specific PAH medication in these patients are lacking, and even worse, these medications may cause harm by further impairing oxygenation. Based on current knowledge optimal therapy of the underlying lung disease and long-term oxygen therapy are the mainstay of therapy. Comorbidities like left heart disease, sleep-related breathing disorders, and pulmonary embolism have to be actively excluded, or if present treated appropriately. Eligible patients should be seen at a lung transplantation and pulmonary hypertension center, where the indication for lung transplantation or criteria for enrollment in a clinical treatment trial are checked. Only in rare individual cases may specific “off-label” therapy of pulmonary hypertension be considered.     

Autoimmune rheumatische Erkrankungen in der Schwangerschaft

Pregnancy is an exceptional state of natural immunomodulation which protects the fetus against the immunological attack by the maternal immune system. The mechanisms of pregnancy-related tolerance may have a positive or negative effect on autoimmune rheumatic diseases. The majority of patients with rheumatoid arthritis experience an improvement in the disease during pregnancy whereas in most ankylosing spondylitis patients the inflammatory back pain remains unchanged. Connective tissue diseases or vasculitis pose a threat to the well-being of both mother and fetus particularly when the activity of the disease is high. In general, pregnancy in patients with rheumatic diseases should be planned in a phase of quiescent disease. Medication compatible with pregnancy should be tailored for the individual patients according to disease activity. A close interdisciplinary observation of these patients is the key for successful pregnancy outcome.     

Pulmonale Hypertonie bei chronischen Lungenerkrankungen

Pulmonary hypertension is a well-known complication of chronic respiratory diseases with an adverse influence on prognosis. While hypoxaemia has been traditionally viewed as the main cause of pulmonary vasoconstriction with a subsequent increase of pulmonary arterial pressure, the importance of pulmonary vasculature remodelling is being increasingly realized. Patients with chronic lung diseases who are suspected of having pulmonary hypertension should be screened by transthoracic echocardiography. A diagnosis of pulmonary hypertension should be verified by right heart catheterization, before a specific therapy is started. Patients newly diagnosed with pulmonary hypertension should undergo spirometry, body plethysmography, arterial blood gas analysis at rest and during exercise as well as a pulmonary CT scan with regard to an underlying disease of the respiratory system. Sleep-related disorders of breathing should be excluded by polysomnography. Long-term oxygen treatment in order to maintain sufficient oxygenation is the key therapy in patients with parenchymal lung disease and pulmonary hypertension. Given the lack of evidence of a beneficial effect, pulmonary vasodilators cannot be recommended for these patients.