Risikostratifizierung ausgewählter schwerer Organbeteiligungen bei Systemischer Sklerose und bei Lupus-Nephritis

Zusammenfassung

Interstitielle Lungenerkrankung (ILD), pulmonal-arterielle Hypertonie (PAH), kardiale Beteiligung und renale Krise sind schwere Prognose-bestimmende Manifestationen der Systemischen Sklerose (SSc). Digitale Ulcerationen führen zu erheblicher Beeinträchtigung von Erwerbsfähigkeit und Lebensqualität. Im Rahmen der Betreuung von SSc-Patienten ist daher eine Risikostratifizierung in Hinblick auf Entwicklung und Progression dieser schweren Manifestationen von wesentlicher Bedeutung. Risikofaktoren für die Entwicklung einer SSc-ILD sind diffuse cutane Sklerodermie (dcSSc), männliches Geschlecht und der Nachweis von Topoisomerase-I-Antikörpern. Ausmaß und Verlauf der SSc-ILD sind variabel. Klinik, Ausgangsbefund und Dynamik der Lungenfunktion und hochauflösendes CT (HR-CT) des Thorax werden genutzt, um frühzeitig Patienten zu identifizieren, welche einer Immunsuppression bedürfen und von jenen zu unterscheiden, bei denen zunächst engmaschige Verlaufskontrollen vertretbar sind. Zu den Risikofaktoren einer SSc-PAH zählen langer Krankheitsverlauf, hohes Lebensalter bei Beginn der SSc, schwere Raynaud-Symptomatik, schwere digitale Ischämien sowie Teleangiektasien, der Nachweis von Centromer-Antikörpern sowie Antikörpern gegen Endothelin-A-Rezeptor und Angiotensin-1-Rezeptor und Hyperurikämie. Bei etablierter PAH erfolgt die Risikostratifizierung auf Basis der kalkulierten 1-Jahres-Mortaliät. Zur Kalkulation der 1-Jahresmortalität werden anamnestische und klinische Parameter wie Symptomprogression, Auftreten von Synkopen, Vorhandensein klinischer Zeichen einer Rechtsherzinsuffizienz, funktionelle WHO-Klasse, funktionsdiagnostische, laborchemische, echokardiografische sowie hämodynamische Parameter herangezogen. Nach den aktuellen Empfehlungen zur Therapie der PAH ist eine primäre Kombinationstherapie zumindest ab WHO-Funktionsklasse III und einem intermediären Risiko (1-Jahres-Mortalität≥5%) indiziert. Wesentliche Risikofaktoren einer kardialen Beteiligung bei SSc sind höheres Lebensalter, dcSSc und der Nachweis von Topoisomerase I-Antikörpern. Zu den Risikofaktoren der renalen Krise bei SSc zählen dcSSc, männliches Geschlecht, der Nachweis von RNA-Polymerase III-Antikörpern, vorbestehende Proteinurie, aber auch eine Vortherapie mit Glukokortikoiden, ACE-Hemmern und Cyclosporin. Digitale Ulcera (DU) treten bei ca. 50% der Patienten auf. Risikofaktoren von DU sind dcSSc, Nachweis von Topoisomerase I-Antikörpern, früher Beginn der Raynaud-Symptomatik, hoher Rodnan Skin Score und männliches Geschlecht. Entscheidendes Therapieziel bei der Lupus-Nephritis (LN) ist der Erhalt einer normalen Nierenfunktion und die Vermeidung einer terminalen Niereninsuffizienz, welche mit einer erhöhten Letalität assoziiert ist. Zu den Risikofaktoren eines ungünstigen Langzeitverlaufs der LN zählen v. a. eine initiale irreversible Nierenfunktionseinschränkung im Zusammenhang mit irreversiblen chronischen Läsionen in der Nierenbiopsie, unzureichend kontrollierte arterielle Hypertonie, ausgeprägte initiale Proteinurie und männliches Geschlecht. Eine effektive Reduktion der Proteinurie auf<0,5–0,8 g/d innerhalb von 12 Monaten nach Beginn der Remissionsinduktion signalisiert dagegen eine günstige Prognose. Frühestmögliche Diagnose der LN und umgehende auf dem Befund der Nierenbiopsie basierende Therapie sowie Reinduktion bei ausbleibender Remission sind entscheidend für eine Minimierung der Risikos.

Abstract

Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac involvement and renal crisis are critical manifestations of systemic sclerosis (SSc) that determine prognosis. Digital ulcers result in substantial impairment of ability to work and quality of life. In the course of management of SSc patients, risk stratification with respect to development and progression of severe manifestations is of critical importance. Risk factors for development of SSc-ILD are diffuse cutaneous scleroderma (dcSSc), male gender and the evidence of topoisomerase I-antibodies. Extent and course of SSc-ILD are variable. Clinical parameters, baseline findings and dynamics of pulmonary function tests and high-resolution CT (HR-CT) are used to identify patients requiring early immunosuppression and distinguish them from patients for whom short-term controls are sufficient. Long disease course, older age at the beginning of SSc, severe Raynaud syndrome and digital ischemia, teleangiectasia, the evidence of centromer antibodies and of antibodies against endothelin A receptor and angiotensin-1 receptor and hyperuricemia are among the factors associated with an increased risk for SSc-PAH. In established PAH, risk stratification is based on calculated 1-year mortality. For calculation of 1-year mortality, historical and clinical parameters such as progression of symptoms, occurrence of syncopes, clinical signs of right heart failure, functional WHO class, clinical chemistry, echocardiographic and haemodynamic findings and results of function tests are used. According to the present recommendations for treatment of PAH, primary combination therapy is indicated at least from WHO functional class III and intermediate risk (1-year mortality>5%). Important risk factors of cardiac involvement in SSc are older age, dcSSc and evidence of topoisomerase I-antibodies. Risk factors for SSc renal crisis include dcSSc, male gender, the evidence of anti-RNA polymerase III antibodies, pre-existing proteinuria but also pre-existing therapy with glucocorticoids, ACE inhibitors and cyclosporine. Digital ulcers (DU) occurs in about 50% of SSc patients. Risk factors of DU are dcSSc, evidence of topoisomerase I-antibodies, early onset Raynaud phenomenon, high Rodnan skin score and male gender. Preservation of renal function and prevention of end-stage renal disease that is associated with increased mortality are important aims of the therapy of lupus nephritis (LN). Risk factors for poor long-term outcome of LN are initial irreversible reduction in renal function in association with irreversible chronic lesions in renal biopsy, uncontrolled arterial hypertension, high initial proteinuria and male gender. On the other hand, effective reduction of proteinuria to<0.5–0.8 g daily within 12 months after start of remission induction indicate a good prognosis. Earliest possible diagnosis of LN and urgent therapy based on the result of renal biopsy and re-induction in the case of no remission are critical for risk minimisation.

Schlüsselwörter

Risikostratifizierung - Systemische Sklerose - Lupusnephritis

Key words

risk stratification - systemic sclerosis - lupus nephritis

Publication History

Article published online:
08 April 2021

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