Lymphangioleiomyomatose

Zusammenfassung

Die LAM ist eine der seltenen Lungenerkrankungen. Sie ist in Deutschland bei 200–400 Patientinnen zu erwarten. Nur sehr vereinzelt wird von möglichen Erkrankungen bei Männern berichtet. Die LAM existiert als spontane LAM (S-LAM) aufgrund einer Mosaikmutation des Tuberin-Gens oder als Keimbahnmutation in Verbindung mit generalisierten Symptomen als tuberöse-Sklerose-assoziierte LAM (TSC-LAM). Obwohl der Einfluss des Östrogens auf die Erkrankung noch unzureichend geklärt ist, verschlechtern Schwangerschaften oder östrogenhaltige Antikonzeptiva den allerdings variablen Verlauf der Erkrankung. Die Prognose für ein 10-Jahres-Überleben liegt nach heutigen Erkenntnissen deutlich über 80 %, aber die Variabilität ist groß.

Es gibt rasch verlaufende, progrediente Erkrankungen. Pneumothorax, Chylothorax und Belastungsdyspnoe beherrschen das klinische Bild. Im CT ist der zystische Umbau des Lungenparenchyms in variablem Ausmaß meist gut erkennbar und charakteristisch. Zellulär ist der mTORC1-Komplex dauerhaft in LAM-Zellen aktiviert und führt zu Proteinsynthese, Proliferation, vermehrtem Gewebsumbau, verbessertem Zellüberleben und auch zur Metastasierung in die Lunge bei eher extrapulmonal vermutetem Ursprung. Nach einer weitgehenden Aufklärung des pathologischen Signalweges wurde mit den mTORC1-Inhibitoren (Sirolimus, Everolimus) ein erster Ansatz einer progressionsaufhaltenden Therapie gefunden und in einer als Meilenstein zu wertenden Studie als wirksam gezeigt. Nach ergänzenden Strategien der Therapie wird derzeit gesucht. Die Prognose der LAM wird dadurch in Zukunft vermutlich eine deutliche Verbesserung erfahren. In therapieresistenten Fällen ist eine Lungentransplantation zu erwägen.

Abstract

LAM is one of the rare lung diseases. Approximately 200–400 female patients are to be expected in Germany. Only rare reports exist describing a male LAM patient. LAM exists in two forms: a spontaneous mosaic mutation (S-LAM) and a germ line mutation resulting in a combination of pulmonary and systemic symptoms called tuberous sclerosis (TSC-LAM). Although the influence of estrogen is not yet entirely recognized, pregnancy and estrogen containing anticonception will worsen the course of the disease. Ten year prognosis of the disease is well over 80 % but variability is large. Rapid progression exists.

The clinical picture of S-LAM is dominated by pneumothorax, chylous pleural effusions, dyspnoea upon exertion. (HR) CT demonstrates the easily recognizable and characteristic cystic transformation of the parenchyma. The cellular sequels of the disease involve constant activation of the mTORC1 complex with protein synthesis, proliferation, enzymatic parenchymal transformation, improved cellular survival and metastasis into the lungs most likely from an extrapulmonary source. Following extensive research on the pathologic activation of the mTORC1 pathway, an initial way of halting progression has been found in using mTORC1 inhibitors (Sirolimus, Everolimus). Complimentary strategies are currently investigated in order to improve the therapeutic effect. These measures will improve LAM prognosis in the future. Therapy resistant LAM is a valid indication for lung transplantation.

Key words

Lymphangioleiomyomatose (LAM) - tuberöse Sklerose - muskuläre Zirrhose der Lunge - genetische Erkrankung - Lungenerkrankung - Pneumothorax - Chylothorax - Belastungsdyspnoe - Lungentransplantation

Key words

Lymphangioleiomyomatosis (LAM) - tuberous sclerosis - lung disease - genetic disease - pneumothorax - chylous pleural effusion - dyspnoea upon exertion - lung transplantation

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