Zusammenfassung
Syndrome mit Hautfragilität gehören zu verschiedenen Gruppen von Genodermatosen: Epidermolysis bullosa, Ehlers-Danlos-Syndromen und Porphyrien. Dabei sind außer dem Integument auch extrakutane Organe oder Systeme primär beteiligt: Herz, Skelettmuskeln, Darm, Nieren, Leber, Gefäße oder das Skelett. Pathogenetisch sind diese Syndrome auf Verlust oder Dysfunktion von Strukturproteinen, die die mechanische Stabilität der Gewebe gewährleisten, zurückzuführen. Vom betroffenen Protein abhängig kann die Hautfragilität zu oberflächlichen Erosionen, Blasenbildung, Wunden, Wundheilungsstörungen oder Vernarbung führen. Im Rahmen der Epidermolysis bullosa gibt es einige syndromale Subtypen, z. B. Hautfragilität mit: 1) Kardiomyopathie, bei Mutationen in den Genen für Desmoplakin, Plakoglobin oder Kelch-like-Protein 24; 2) Muskeldystrophie bei Mutationen im Plektin-Gen; 3) Pylorusatresie bei Verlust von Integrin α6β4 oder Plektin; 4) primäre Nierenbeteiligung in Form eines nephrotischen Syndroms oder Malformationen bei CD151 oder Integrin-α3-Mutationen. Mutationen im Gen für Lysylhydroxylase 3 stören die posttranslationale Modifikation von Kollagenen und verursachen eine komplexe systemische Erkrankung, die der dystrophen Epidermolysis bullosa ähnlich ist. Defekte der Kollagene im Bindegewebe inklusive der Dermis führen zu verschiedenen Formen der Ehlers-Danlos-Syndrome mit Gefäß- und Gelenkbeteiligung. Schließlich sind die Porphyrien eine Gruppe komplexer metabolischer Erkrankungen mit Hautfragilität, Photosensitivität sowie auch neurologischer oder hepatischer Beteiligung. Vermutlich beruht die Pathogenese auf der Akkumulation von Häm-Vorstufen. In der Praxis sind diese Erkrankungen sehr selten. Allerdings ist es wichtig, an die mögliche syndromale Konstellation zu denken, um den Weg zur Diagnose zu verkürzen und mögliche Komplikationen frühzeitig zu erkennen.
Abstract
Syndromic disorders with skin fragility belong to different groups of genodermatoses: epidermolysis bullosa (EB), Ehlers–Danlos syndrome and porphyria. The genetic defects mainly concern structural proteins which assure the mechanical stability of the skin and other tissues. Depending on the expression pattern of the affected protein in the skin, cutaneous fragility may manifest as superficial erosions, blisters, wounds, wound healing defects or scars. Extracutaneous manifestations are manifold and involve the heart, skeletal muscles, intestine, kidneys, blood vessels or the skeleton. Syndromic types of EB include in addition to skin blistering: (i) cardiomyopathy in case of desmoplakin, plakoglobin, or kelch-like protein mutations; (ii) muscular dystrophy in case of plektin mutations; (iii) pyloric atresia in case of integrin α6β4 or plectin mutations; (iv) nephrotic syndrome in case of CD151 or integrin α3 mutations. Lysyl hydroxylase 3 mutations affect posttranslational modifications of collagens and lead to a dystrophic epidermolysis bullosa-like multisystemic disorder. Ehlers–Danlos syndromes are due to defects of dermal collagens or their processing and affect the skin, joints and blood vessels. Finally porphyrias are complex metabolic disorders with photosensitivity and sometimes skin fragility, liver or neurologic problems. Their pathogenesis relies on the accumulation of precursors in the tissues. Although these syndromes are rare in clinical practice, knowledge of the syndromic constellation contributes to early diagnosis and detection of complications.
Abbreviations
- CEP:
-
kongenitale erythropoetische Porphyrie
- DEB:
-
dystrophe Epidermolysis bullosa
- EB:
-
Epidermolysis bullosa
- EBJ:
-
Epidermolysis bullosa junctionalis
- EBJ-PA:
-
Epidermolysis bullosa junctionalis mit Pylorusatresie
- EBS:
-
Epidermolysis bullosa simplex
- EBS-MD:
-
Epidermolysis bullosa simplex mit Muskeldystrophie
- EDS:
-
Ehlers-Danlos-Syndrom
- EPP:
-
erythropoetische Protoporphyrie
- DEJ:
-
dermoepidermale Junktionszone
- ILNEB:
-
interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa
- RDEB:
-
rezessive dystrophe Epidermolysis bullosa
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C. Has ist Mitglied des ERN-Skin. A. Reimer erhält eine Förderung durch das Berta-Ottenstein-Programm für Clinician Scientists der Medizinischen Fakultät der Albert-Ludwigs-Universität Freiburg.
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Reimer, A., Has, C. Syndrome mit Hautfragilität. Hautarzt 70, 481–489 (2019). https://doi.org/10.1007/s00105-019-4433-5
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DOI: https://doi.org/10.1007/s00105-019-4433-5