Lungenbeteiligung im Rahmen der IgG4-assoziierten Erkrankungen

Zusammenfassung

Immunoglobulin G4-assoziierte Erkrankungen (IGAE) sind eine vor kurzem definierte und an Wichtigkeit zunehmende Entität. Sie charakterisiert sich durch die Bildung von inflammatorischen Reaktionen, reich an IgG4-positiven Plasmazellen, begleitet von einer Fibrosklerose und einer obliterativen Phlebitis. In der immunohistochemischen Färbung zeigen sich erhöhte IgG4-positive Zellen in den betroffenen Organen. Im Serum finden sich erhöhte IgG, sowie IgG4-Spiegel, welche der Erkrankung den Namen gaben. Die IGAE betreffen Patienten in den mittleren und älteren Jahren, mit einer männlichen Prädominanz. Der Prototyp ist die autoimmune Pankreatitis (AIP), dort wurde die Diagnose einer IGAE zum ersten Mal gestellt. Mögliche Manifestationen der IgG4-assoziierten Erkrankungen sind retroperitoneale Fibrose, Dakryoadenitis, Sialadenitis, Thyroiditis, Pneumonitis, Pankreatitis, sklerosierende Cholangitis, Nephritis, Otitis media, Aortitis, Periaortitis, Prostatitis und Hypophysitis [1] [2]. Nicht selten findet sich auch eine Beteiligung mehrerer Organsysteme beim gleichen Patienten. In der Lunge können das Parenchym, der Pleuraraum, das Mediastinum, sowie die Luftwege betroffen werden. Zur Diagnosesicherung ist eine Biopsie, vorzugsweise eine chirurgische Resektion, zwingend erforderlich. Eine PET/CT Untersuchung kann bei Patienten mit einer IGAE sinnvoll sein, um einen Überblick über den Organbefall zu bekommen, sowie um die beste Biopsieentnahmestelle zu lokalisieren. IGAE sprechen in der Regel gut auf die Behandlung mit Glukokortikoiden an, es kann jedoch unter einer Glukokorticoid-Monotherapie zu Rückfällen kommen. Unter der Behandlung mit Glukokortikoiden kommt es häufig zu einem Absinken der Serum IgG4-Spiegel. Es gibt wenige Veröffentlichungen, die den Gebrauch von pharmakologischen Substanzen außer Kortikosteroiden beschreiben. Eine adjunktive Therapie mit Bortezomib, sowie Cyclosporin könnte sich als vielversprechend erweisen. Bis jetzt wurde in der Literatur keine Spontanheilung der intrathorakalen IGAE beschrieben. Es gibt leider keine weiteren Information zu anderen Immunsuppressiva bei Lungenbefall im Rahmen einer IGAE, jedoch wurden Azathioprin, Mycophenolat, Methotrexat und Cyclophosphamid manchmal benutzt um einem Langzeitrückfall bei dem Befall von extrapulmonalen Organen vorzubeugen. Die Natur, sowie die Pathogenese der IGAE sind zum jetzigen Zeitpunkt weitestgehend unbekannt und bieten somit einen großen Forschungsbedarf.

Abstract

Immunoglobulin G4-related systemic disease (IRSD) is a recently defined and emerging entity characterized by a diffuse or mass forming inflammatory reaction, rich in IgG4-positive plasma cells, associated with fibrosclerosis and obliterative phlebitis. Affected organs are found to exibit an increased number of IgG4-positive cells. In the serum, raised IgG and IgG4-levels are found, which acts as a marker for this recently characterized entity. IRSD affects patients in midlle and older age, with a male predominance. The prototype of the disease is the autoimmune pancreatitis (AIP), being the first organ to be diagnosed with an IRSD. Possible manifestations of the IRSD are retroperitoneal fibrosis, dacryoadenitis, sialadenitis, thyroiditis, pneumonitis, pancreatitis, sclerosing cholangitis, nephritis, otitis media, aortitis, periaortitis, prostatitis, and hypophysitis. Often manifestations of several organs can be found in the same patient. In the lung, IRSD can affect the parenchyma, the pleura, the mediastinum as well as the airways. In order to diagnose an IRSD, a biopsy, preferably a surgical resection is necessary. Positron emission tomography with computer tomography (PET/CT) can provide an overview of the organs being involved, as well as localizing the best site for biopsy. IRSD normally responds well to glucocorticosteroids, nevertheless under glucocorticoid monotherapy a relapse can occur. During therapy with glucocorticosteroids, serum IgG4-levels decline. There are few reports, which describe the use of pharmacological substances other than corticosteroids. An adjunctive therapy with Bortezomib, as well as cyclosporine seems to be promising. Until now, no spontaneous healing of a intrathoracic IRSD was described. Unfortunately no further data about other immunosuppressants and lung involvement in IRSD are available, however azathioprin, mycophenolat, methotrexat and cyclophosphamide were sometimes used in order to prevent a longtime relapse in patients with extrapulmonary disease. However, the nature and pathogenesis of RSD are yet to be fully elucidated and provide immense scope for further research.

Schlüsselwörter

IgG4 assoziierte Erkrankungen - Pulmonale Infiltrate - Interstitielle Lungenerkrankung - Lymphadenopathie

Key words

IgG4 related systemic disease - Pulmonary infiltrates - Interstitial lung disease - Lymphadenopathy

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