Koronare Herzerkrankung bei HIV-positiven Patienten: Einfluss der antiretroviralen Therapie

The use of highly antiretroviral therapy (HAART) significantly reduced morbidity and mortality by inhibition of virus replication. Even though long-term side effects are not fully known, this antiviral strategy has revolutionized the care of HIV-infected patients and is widely used in industrial countries.Until now, a variety of metabolic side effects, such as hyperlipidemia and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy increase the cardiovascular risk profile of HIV-infected patients. It could be expected, that the increased cardiovascular risk profile in combination with long-term survival of this patient population, will increase the diagnostics and therapy of coronary diseases of HIVinfected patients in the next years.The present article (1) contains the case report of a 39-year-old HIV-infected male with an acute myocardial infarction, and (2) gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.     

Direkte und indirekte atherogene Effekte der HIV-Infektion und antiretroviralen Therapie

Highly active antiretroviral therapy (HAART) has led to a significant decrease in HIV-associated morbidity and mortality. Clinical data, however, suggest that both HIV infection and HAART may be associated with an increased cardiovascular risk. A variety of excellent review articles have been published on clinical evidence regarding cardiovascular events in HIV-positive and HAART-treated patients. The underlying mechanisms of the cellular and metabolic alterations in HIV-infected patients remain unclear. This article outlines the general pathogenesis of atherosclerosis and describes the potential role of HIV infection and antiretroviral therapy on direct and indirect effects in atherogenesis.     

Nebenwirkungen der medikament?sen Therapie rheumatischer Erkrankungen am Nervensystem

Antirheumatic medication is of crucial importance within the treatment concept of chronic inflammatory disorders. Side effects may affect various organ systems, among which are neurologic manifestations. If patients have comorbidities involving the nervous system this should be taken into consideration before choosing an individual immunosuppressant or immunomodulatory compound, as any worsening of the underlying neurologic disease should be avoided. In this article, relevant neurologic disorders will be described with respect to the clinical manifestations, differential diagnosis and treatment. In the second part, pharmaceuticals and biologicals which are frequently used as part of an antirheumatic regimen are discussed with respect to the potential to induce side effects specifically related to the nervous system.     

Nebenwirkungen der medikament?sen Tumortherapie

Cytotoxic drugs have been used in the therapy of malignant tumors for the last 70?years. However, side effects of cytotoxic drugs are very common and often dose-limiting. Although many protocols have been optimized, side effects are still frequently life-threatening. Nausea and vomiting are among the most frequently reported side effects, in addition to mucositis and fatigue. Bone marrow toxicity can lead to neutropenic sepsis, thrombocytopenic bleeding, or anemia with the respective sequelae. In addition to these unspecific side effects, organ toxicity is class or drug specific and may involve the kidney, liver, heart, lung, skin, or central nervous system. As most protocols can be administered on an outpatient basis, knowledge of these side effects is important for the general internist.     

Interferon-αWirkung, Indikationen, Therapieüberwachung und Nebenwirkungen

Die Therapie mit Interferonen, insbesondere Interferon-α, hat in den letzten Jahren in der Behandlung chronischer Virusinfektionen sowie maligner Erkrankungen zunehmende Bedeutung erlangt. Der Behandlungserfolg ist jedoch nicht selten durch dosisabh?ngige, aber auch dosisunabh?ngige Nebenwirkungen limitiert. Selbst bei Beachtung der Kontraindikationen für eine Interferon-α-Therapie stellt sich mitunter die Frage, ob einer Nebenwirkung durch eine Dosisreduktion begegnet werden kann oder ein Therapieabbruch unumg?nglich ist bzw. ob die Nebenwirkung nach Absetzen der Therapie reversibel ist.     

Analyse von Kosten und Nebenwirkungen der Membranplasmaseparationsbehandlung

Zusammenfassung In der aktuellen Diskussion um das ad?quate Therapieverfahren (intraven?se Immunglobulintherapie vs. Plasmaseparation) beim akuten Guillain-Barré-Syndrom (GBS) besteht derzeit kein allgemeingültiger Konsens. Die vorliegende Untersuchung über Komplikationsh?ufigkeit resp.-schwere von 155 Plasmaseparationen und die Kostenevaluierung beider Verfahren leistet hierzu einen Beitrag. In 27% aller Plasmaaustauschtherapien wurden Ereignisse wie allergische Symptome (5%), Atemnot (3,9%), Unruhe (3,9%) Rhythmusst?rungen (3,2%), Wadenkr?mpfe (2,6%) u.a. beobachtet. 12,5% aller Ereignisse lassen sich auf das Plasmaseparationsverfahren (PS) zurückführen, aber keines dieser stellte eine ernsthafte Gefahr für die Patienten dar. Es zeigen sich signifikante Laborver?nderungen unmittelbar im Anschlu? an die PS (Gesamtkalzium, Antithrombin III, Thrombozyten (p=0,003), die jedoch klinisch bedeutungslos sind. Die Kosten beider Verfahren belaufen sich auf etwa 6500 bis 7000 DM, exklusive Arbeitszeit (Stand: April 1997). Eine Therapie mit intraven?sen Immunglobulinen ist technisch weniger aufwendig als eine Plasmaseparation (PS). Die Kosten belaufen sich in etwa gleich. In dieser Untersuchung traten bei der PS keine ernsthaften Nebenwirkungen auf. Eingegangen: 10. Mai 1998 Akzeptiert: 30. Mai 1998     

Therapie der Achalasie

The treatment of achalasia consists of three basic concepts: surgical myotomy, endoscopic and medical treatment. Endoscopic balloon dilation (EBD) with the option of redilation in cases of recurrence and laparoscopic Heller myotomy (LHM) have shown good long-term efficacy. At 2 years after initial treatment EBD and LHM have similar remission rates but the long-term results show an advantage for surgical myotomy. Peroral endoscopic myotomy (POEM) has the potential to combine the best of both worlds. The access trauma is minimal and potentially it could achieve the long-term results of surgical myotomy. Preliminary results demonstrate good success rates similar to those which can be achieved with EBD and LHM. The intervention can be performed with commercially available endoscopic instruments and complication rates in reported pilot studies are low.     

Therapie der Glomerulonephritis

Zusammenfassung Die Therapie der Glomerulonephritis ist kompliziert, weil das klinische Bild sehr unterschiedlich sein kann. Eine akute Nephritis, ein nephrotisches Syndrom oder lediglich eine geringe Proteinurie oder Hämaturie können Ausdruck einer Glomerulonephritis sein. Die Indikation zu einer symptomatischen Therapie kann vom klinischen Bild abgeleitet werden, eine immunsuppressive Therapie setzt eine histologische Diagnose voraus, um die mögliche Differenzialtherapie abzudecken.Die sofortige Therapie einer rapid-progressiven Glomerulonephritis kann den Patienten vor der Dialyse bewahren. Ein nephrotisches Syndrom wird entsprechend dem klinischen Verlauf zuerst symptomatisch; bei histologischen oder klinischen Anzeichen für eine Progression in die Niereninsuffizienz ist meist eine definierte Immunsuppression zusätzlich indiziert. Die durch Studien untersuchten Therapieschemata werden detailliert vorgestellt.

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Therapie der Lungenfibrose

Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor prognosis. The IFIGENIA trial showed that antioxidative therapy with N-acetylcysteine versus placebo for patients under treatment with prednisone plus azathioprine significantly slowed the deterioration of pulmonary function after 12?months. A number of other drugs have recently been evaluated in large multicenter placebo-controlled trials. Etanercept, interferon-γ, bosentan, ambrisentan, imatinib, and sildenafil did not show efficacy. The antifibrotic active ingredient pirfenidone is the first drug approved for the treatment of adult patients with mild to moderate idiopathic pulmonary fibrosis in the European Union. Approval was based on the results of 4 randomized, placebo-controlled clinical trials including more than 1,100 patients. Pirfenidone slowed the decline in lung function and reduced the risk of disease progression. Side effects include gastrointestinal discomfort, skin reactions, including photosensitivity, and rarely increased liver enzymes.     

Therapie der Systemmykosen

Zusammenfassung Vor Einleitung einer spezifischen antimykotischen Therapie müssen die anamestischen Angaben, die Grundkrankheit und die möglichen therapeutischen Komplikationen überprüft werden, da Mykosen der inneren Organe uncharakteristische Krankheitsbilder darstellen. Besonders bakteriologische Superinfektionen und die Tuberkulose müssen ausgeschlossen werden. Die Chemotherapie der generalisierten Mykosen hat in letzter Zeit große Fortschritte gemacht. Als große Bereicherung des therapeutischen Rüstzeuges ist das 5-Fluorocytosin anzusprechen, das relativ wenig Nebenwirkungen aufweist. Aber auch das gefürchtete Amphotericin B kann bei entsprechend sorgfältiger Handhabung beim gleichen Patienten während Jahren immer wieder mit Erfolg eingesetzt werden, ohne daß beträchtliche Nebenerscheinungen auftreten. Im Gegensatz zur bakteriellen Infektion spielt das Terrain bei der mykotischen Infektion eine weit größere Rolle. Die In-vitro-Resultate müssen mit größter Vorsicht interpretiert werden, da bei den tiefen Mykosen infolge schlechter Vaskularisierung so hohe Blutspiegel erreicht werden müssen, daß die Substanzen zu viele toxische Nebenwirkungen aufweisen. Oft ist der Arzt dafür verantwortlich, daß sich das Terrain so verändert, daß sich eine Mykose entwickeln kann. Wir empfehlen deshalb strengere Indikation für kombinierte Langzeitbehandlungen, ferner bessere Überwachung von Kathetern, Infusionen und medizinischen Geräten, ferner die prophylaktische lokale Anwendung von Mycostatin im Bereiche von Kontaktstellen, um eventuelle Eintrittspforten abzuriegeln.

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Treatment of systemic mycosis

Summary Before commencing a specific antimycotic treatment, the anamnestic data, the underlying disease and possible therapeutic complications must be considered as mycosis of the internal organs can present an uncharacteristic clinical picture. In particular bacterial superinfections and tuberculosis must be excluded. Great progress has been made in recent times with the chemotherapy of generalised mycosis, one of the greatest advances being the introduction of 5-fluorocytosin which has relatively few side-effects. With careful management, however, the formidable amphotericin B can also be administered successfully over a number of years to the same patients without the occurrence of marked side-effects. In contrast to bacterial infections, the site of infection is a much more important factor in mycosis. In-vitro results must be interpreted with great caution since, as a result of poor vascularisation, high blood concentrations are essential in deepseated mycosis and result in too many toxic side-effects. The clinician is often responsible for predisposing conditions which allow the development of a mycosis. We therefore recommend stricter indications for long-term antibiotic treatment, improved supervision of catheters, intravenous therapy and medical equipment. Furthermore, the local application of Nystatin around the contact area is recommended as prophylaxis in order to protect possible points of entry.

     

Therapie der Beinvenenthrombose

Current antithrombotic therapy of deep vein thrombosis (DVT) consists of an initial course of heparin, followed by the secondary prevention with oral anticoagulation (OAC). Low molecular weight heparin has several advantages over unfractionated heparin, however, renal insufficiency has to be observed to avoid accumulation. The synthetic pentasaccharide Fondaparinux is a factor Xa inhibitor, that will shortly be available for the initial treatment of DVT. Oral anticoagulation with vitamin K antagonists (VKA) is highly effective, the standard target INR is 2.0-3.0. For a first episode of DVT the duration of OAC usually is six months, but has to be adjusted according to the estimated risk for recurrence. Because of the narrow therapeutic window of VKA, low molecular weight heparins are increasingly being used for secondary prevention in patients with an increased risk for bleeding, mostly in 1/2-therapeutic dose. At present, several new antithrombotic agents are being studied and may become available shortly for DVT treatment.     

Therapie der Myositiden

Idiopathic inflammatory myopathy consists of dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). At all stages of myositis, physiotherapy is effective in improving muscle strength, endurance and in maintaining joint motion. In DM and PM the therapy is initiated with glucocorticosteroids. Steroid-sparing agents (azathioprine, methotrexate and cyclosporin A) are added to prevent Cushing’s syndrome or an unsatisfactory response. Therapy can also be escalated with intravenous immunoglobulins. Tacrolimus and mycophenolate mofetil (MMF) were effective in small case series. Cyclophosphamide is restricted to patients not responding to previous agents. For treatment intensification immunoglobulins can also be combined with MMF. There is not enough evidence to routinely recommend rituximab. The results with TNF-alpha inhibitors and plasmapheresis were negative or inconsistent. In DM skin involvement responds to sun blockers, antimalarials, topical corticosteroids or calcineurin inhibitors. In NAM statins should be discontinued and treatment with prednisone and immunosuppressants initiated. In IBM a therapeutic trial with prednisone, methotrexate or azathioprine may be warranted, especially in cases in which the serum creatine kinase (CK) is elevated or an inflammatory infiltrate is present in the muscle biopsy.     

Therapie der Psoriasisarthritis

In psoriatic arthritis (PsA) the heterogeneous spectrum of the disease with arthritis/synovitis, axial manifestation, enthesitis, dactylitis, psoriatic skin disease and nail psoriasis has to be considered. Moreover, PsA activity and severity as well as comorbidities are of importance for making therapeutic decisions. Measurement instruments developed for therapeutic studies of rheumatoid arthritis or ankylosing spondylitis are often not appropriate for application in PsA investigations. In this paper established therapies with nonsteroidal antirheumatic drugs, disease modifying antirheumatic drugs (DMARDs) and TNF-alpha inhibitors and the current EULAR guidelines from 2012 are reviewed. However, there is a need for new therapeutic agents for those patients who do not respond to or do not tolerate the current therapies. Other biologic agents have also been tested for PsA with moderate effects only. New therapeutic options could result from the anti-IL12 and anti-IL23 receptor monoclonal antibody ustekinumab and from small molecules such as the oral PDE-4 inhibitor apremilast.